{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:48:27Z","timestamp":1791953307711,"version":"4.3.4"},"reference-count":148,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003417","name":"Deutsche Gesetzliche Unfallversicherung","doi-asserted-by":"publisher","award":["FB 0345"],"award-info":[{"award-number":["FB 0345"]}],"id":[{"id":"10.13039\/501100003417","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FB 0345"],"award-info":[{"award-number":["FB 0345"]}],"id":[{"id":"https:\/\/ror.org\/01agh0847","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The high\u2014and in most countries steadily increasing\u2014incidence of cutaneous squamous cell carcinoma (cSCC) represents a growing public health challenge. As the majority of cSCCs arise from pre-existing actinic keratosis (AKs), these lesions are recognized as the principal precursors of invasive disease. A comprehensive understanding of the molecular mechanisms driving the progression from AK to cSCC is essential for advancing prevention, facilitating early diagnosis, and enabling targeted therapies. Moreover, this knowledge provides a basis for identifying biomarkers that can predict the risk of malignant transformation. The progression from AK to cSCC is a complex, multistep process driven by the gradual accumulation of genetic, epigenetic, and microenvironmental alterations. Over the past decades, numerous molecular changes associated with this transition have been identified. However, no single biomarker has demonstrated sufficient predictive accuracy for clinical use. This reflects the pronounced molecular heterogeneity of AKs as no individual alteration is uniformly present in all lesions that undergo malignant progression. In addition, numerous proposed biomarkers are also detected in non-progressive AKs and even in non-neoplastic skin, which compromises their sensitivity and specificity for predicting progression to cSCC. Current evidence, therefore, suggests that the most promising strategy for identifying AKs at greatest risk of malignant transformation is the development of a multi-marker panel. This panel, ideally, should integrate molecular signatures encompassing genetic, epigenetic, proliferative, inflammatory, and microenvironmental markers. This review summarizes the molecular factors that currently represent the most promising candidates for inclusion in such a multi-marker panel and discusses their potential clinical utility, while emphasizing the need for validation in well-designed prospective longitudinal studies.<\/jats:p>","DOI":"10.3390\/cancers18193221","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:28:05Z","timestamp":1791296885000},"page":"3221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Molecular Alterations to Risk Prediction: Biomarkers of Actinic Keratosis Progression to Cutaneous Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-3809","authenticated-orcid":false,"given":"Thomas","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Dermatology, St. Josef Hospital, Ruhr University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Stockfleth","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Josef Hospital, Ruhr University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-4979","authenticated-orcid":false,"given":"Heiko U.","family":"K\u00e4fferlein","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9560-5464","authenticated-orcid":false,"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eggert","family":"Stockfleth","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Josef Hospital, Ruhr University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1001\/jamadermatol.2015.1187","article-title":"Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012","volume":"151","author":"Rogers","year":"2015","journal-title":"JAMA Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.14336\/AD.2017.0503","article-title":"Skin Cancer Epidemics in the Elderly as An Emerging Issue in Geriatric Oncology","volume":"8","author":"Garcovich","year":"2017","journal-title":"Aging Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0140-6736(09)61196-X","article-title":"Non-melanoma skin cancer","volume":"375","author":"Madan","year":"2010","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.mayocp.2017.02.015","article-title":"Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: A population-based study in Olmsted County, Minnesota, 2000 to 2010","volume":"92","author":"Muzic","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nanz, L., Keim, U., Katalinic, A., Meyer, T., Garbe, C., and Leiter, U. (2024). Epidemiology of Keratinocyte Skin Cancer with a Focus on Cutaneous Squamous Cell Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16030606"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1001\/jamadermatol.2025.5700","article-title":"Incidence Trends of Cutaneous Squamous Cell Carcinoma, Carcinoma In Situ, and Keratoacanthoma By Sex, Age, and Anatomical Site","volume":"162","author":"Duffau","year":"2026","journal-title":"JAMA Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejca.2023.01.017","article-title":"Incidence, mortality and trends of cutaneous squamous cell carcinoma in Germany, the Netherlands, and Scotland","volume":"183","author":"Keim","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116068","DOI":"10.1016\/j.ejca.2025.116068","article-title":"Cutaneous squamous cell carcinoma 1986-2019 in Germany: Incidence, anatomical site, staging, and histologic subtypes","volume":"230","author":"Balkenhol","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.5694\/mja17.00284","article-title":"The incidence and multiplicity rates of keratinocyte cancers in Australia","volume":"207","author":"Pandeya","year":"2017","journal-title":"Med. J. Aust."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/jdv.15967","article-title":"Incidence and mortality for cutaneous squamous cell carcinoma: Comparison across three continents","volume":"33","author":"Stang","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1001\/jamadermatol.2026.0964","article-title":"Global Skin Cancer Burden From 1990 to 2023 and Projection to 2050","volume":"162","author":"Zhou","year":"2026","journal-title":"JAMA Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1001\/jamadermatol.2013.2139","article-title":"Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: A 10-year, single-institution cohort study","volume":"149","author":"Schmults","year":"2013","journal-title":"JAMA Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/jdv.19559","article-title":"Actinic keratosis: Current challenges and unanswered questions","volume":"38","author":"Malvehy","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/ijd.14147","article-title":"Actinic keratosis\u2014Review for clinical practice","volume":"58","author":"Pantoja","year":"2019","journal-title":"Int. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jdv.14151","article-title":"From actinic keratosis to squamous cell carcinoma: Pathophysiology revisited","volume":"31","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1093\/bjd\/ljad174.002","article-title":"002 neoantigens from actinic keratosis are predicted to be more immunogenic than those from cutaneous squamous cell carcinoma\u2014A strategy for immune escape","volume":"189","author":"Thomson","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jaad.2020.03.126","article-title":"Field cancerization: Definition, epidemiology, risk factors, and outcomes","volume":"83","author":"Willenbrink","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/bjd.12420","article-title":"The natural history of actinic keratosis: A systematic review","volume":"169","author":"Werner","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1067\/mjd.2000.103339","article-title":"The risk of progression to invasive disease","volume":"42","author":"Glogau","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S0140-6736(88)91658-3","article-title":"Malignant transformation of solar keratoses to squamous cell carcinoma","volume":"331","author":"Marks","year":"1988","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/cncr.24284","article-title":"Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial","volume":"115","author":"Criscione","year":"2009","journal-title":"Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/1097-0215(20010120)95:1<7::AID-IJC1001>3.0.CO;2-X","article-title":"Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults","volume":"95","author":"Foote","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/bjd.18338","article-title":"The clinical course of actinic keratosis correlates with underlying molecular mechanisms","volume":"182","author":"Bakshi","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, Z., Lu, F., Zhou, F., Song, D., Chang, L., Liu, W., Yan, G., and Zhang, G. (2025). From actinic keratosis to cutaneous squamous cell carcinoma: The key pathogenesis and treatments. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1518633"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-2133.2010.10118.x","article-title":"Occupational ultraviolet light exposure increases the risk for the development of cutaneous squamous cell carcinoma: A systematic review and metaanalysis","volume":"164","author":"Schmitt","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/jdv.12102","article-title":"Prevalence and risk factors of actinic keratoses in Germany\u2013analysis of multisource data","volume":"28","author":"Schaefer","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13555-015-0070-9","article-title":"Primary care review of actinic keratosis and ist therapeutic options: A global perspective","volume":"5","author":"Chetty","year":"2015","journal-title":"Dermatol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1684\/ejd.2017.3126","article-title":"Prevalence and risk factors of actinic keratosis in patients attending italian dermatology clinics","volume":"27","author":"Fargnoli","year":"2017","journal-title":"Eur. J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0190-9622(95)90239-2","article-title":"Comparative epidemiologic study of premalignant and malignant epithelial cutaneous lesions developing after kidney and heart transplantation","volume":"33","author":"Euvrard","year":"1995","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_30","first-page":"513","article-title":"Incidence of skin cancer in 5356 patients following organ transplantation","volume":"143","author":"Lindelof","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1056\/NEJMra022137","article-title":"Skin cancers after organ transplantation","volume":"348","author":"Euvrard","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/17401","article-title":"Cyclosporine induces cancer progression by a cell-autonomous mechanism","volume":"397","author":"Hojo","year":"1999","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/978-3-642-59410-6_30","article-title":"Epithelial malignancies in organ transplant patients: Clinical presentation and new methods of treatment","volume":"160","author":"Stockfleth","year":"2002","journal-title":"Recent Results Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/jdv.14092","article-title":"The importance of treating the field in actinic keratosis","volume":"31","author":"Stockfleth","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jaad.2017.08.059","article-title":"Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging","volume":"78","author":"Que","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"116763","DOI":"10.1016\/j.ejca.2026.116763","article-title":"European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention\u2014Update 2026","volume":"243","author":"Stratigos","year":"2026","journal-title":"Eur. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41586-019-1719-9","article-title":"Immunity to commensal papillomaviruses protects against skin cancer","volume":"575","author":"Strickley","year":"2019","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dervenis, V. (2025). The Role of HPV in the Development of Cutaneous Squamous Cell Carcinoma-Friend or Foe?. Cancers, 17.","DOI":"10.3390\/cancers17071195"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1093\/bjd\/ljag016","article-title":"Presence of koilocytes in actinic keratosis identifies those at high risk of developing keratinocyte carcinoma","volume":"194","author":"Morgan","year":"2026","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.jid.2017.03.027","article-title":"Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma","volume":"137","author":"Dusingize","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2133.2007.07860.x","article-title":"Actinic keratosis is an early in situ squamous cell carcinoma: A proposal for reclassification","volume":"156","author":"Patel","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/jdv.12848","article-title":"Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin","volume":"29","author":"Carrato","year":"2015","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/jdv.14512","article-title":"Actinic keratoses show variable histological basal growth patterns\u2014A proposed classification adjustment","volume":"32","author":"Schmitz","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1111\/jdv.15580","article-title":"Evaluation of two histological classifications for actinic keratoses\u2014PRO classification scored highest inter-rater reliability","volume":"33","author":"Schmitz","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Schmitz, L., Falkenberg, C., Balkenhol, J., Melzer, P., Philipp-Dormston, W.G., and Dirschka, T. (2025). Clinical Olsen Grading Does Not Reflect Basal Growth in Actinic Keratoses: Two-Center Retrospective Analysis. Cancers, 17.","DOI":"10.3390\/cancers17233794"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/372773a0","article-title":"Sunburn and p53 in the onset of skin cancer","volume":"372","author":"Ziegler","year":"1994","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Piipponen, M., Riihila, P., Nissinen, L., and Kahari, V.M. (2021). The role of p53 in progression of cutaneous squamous cell carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13184507"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"325","DOI":"10.4103\/0019-5154.113935","article-title":"Reduced P53 Staining in Actinic Keratosis is Associated with Squamous Cell Carcinoma: A Preliminary Study","volume":"58","author":"Neto","year":"2013","journal-title":"Indian J. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hedberg, M.L., Berry, C.T., Moshiri, A.S., Xiang, Y., Yeh, C.J., Attilasoy, C., Capell, B.C., and Seykora, J.T. (2022). Molecular mechanisms of cutaneous squamous cell carcinoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073478"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1073\/pnas.91.1.360","article-title":"UV and skin cancer: Specific p53 gene mutation in normal skin as a biologically relevant exposure measurement","volume":"91","author":"Nakazawa","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.1097\/PGP.0000000000000488","article-title":"Interpretation of p53 immunohistochemistry in endometrial carcinomas: Toward increased reproducibility","volume":"38","author":"Ronnett","year":"2019","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00403-020-02104-y","article-title":"P53 staining index and zonal staining patterns in actinic keratoses","volume":"313","author":"Javor","year":"2021","journal-title":"Arch. Dermatol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41418-018-0246-9","article-title":"Mutant p53 as a guardian of the cancer cell","volume":"26","author":"Mantovani","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1038\/s41388-023-02859-4","article-title":"p63: A crucial player in epithelial stemness regulation","volume":"42","author":"Li","year":"2023","journal-title":"Oncogene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nrc3446","article-title":"p63 steps into the limelight: Crucial roles in the suppression of tumorigenesis and metastasis","volume":"13","author":"Su","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.0303-6987.2004.00228.x","article-title":"Expression profiles of p63, p53, survivin, and hTERT in skin tumors","volume":"31","author":"Park","year":"2004","journal-title":"J. Cutan. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/ncb1420","article-title":"p63 regulates an adhesion programme and cell survival in epithelial cells","volume":"8","author":"Carroll","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1007\/s00018-020-03539-2","article-title":"TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development","volume":"77","author":"Yi","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/sj.cr.7290257","article-title":"Activation and signaling of the p38 MAP kinase pathway","volume":"15","author":"Zarubin","year":"2005","journal-title":"Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.bbamcr.2007.03.010","article-title":"p38 MAP-Kinases pathway regulation, function and role in human diseases","volume":"1773","author":"Cuenda","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41580-020-00322-w","article-title":"Diversity and versatility of p38 kinase signalling in health and disease","volume":"22","author":"Canovas","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrc.2016.145","article-title":"Notch as a tumour suppressor","volume":"17","author":"Nowell","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1101\/gad.1477606","article-title":"Canonical notch signaling functions as a commitment switch in the epidermal lineage","volume":"20","author":"Blanpain","year":"2006","journal-title":"Genes Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ceb.2008.01.010","article-title":"Epidermal Notch signalling: Differentiation, cancer and adhesion","volume":"20","author":"Watt","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.semcancer.2004.04.017","article-title":"Notch signaling in the integrated control of keratinocyte growth\/differentiation and tumor suppression","volume":"14","author":"Lefort","year":"2004","journal-title":"Semin. Cancer Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1038\/onc.2008.225","article-title":"Notch tumor suppressor function","volume":"27","author":"Dotto","year":"2008","journal-title":"Oncogene"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/35096061","article-title":"The INK4a\/ARF network in tumour suppression","volume":"2","author":"Sherr","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrc3960","article-title":"Forging a signature of in vivo senescence","volume":"15","author":"Sharpless","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc2772","article-title":"Senescence in tumours: Evidence from mice and humans","volume":"10","author":"Collado","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0304-3835(01)00757-1","article-title":"Progression of actinic keratosis to squamous cell carcinoma of the skin correlates with deletion of the 9p21 region encoding the p16(ink4a) tumor suppressor","volume":"176","author":"Mortier","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1002\/ijc.24871","article-title":"Cdkn2a but not tp53 mutations nor hpv presence predict poor outcome in metastatic squamous cell carcinoma of the skin","volume":"126","author":"Verdijk","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1038\/s41467-018-06027-1","article-title":"The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature","volume":"9","author":"Inman","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1535-6108(02)00102-2","article-title":"The RB and p53 pathways in cancer","volume":"2","author":"Sherr","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1155\/2007\/942650","article-title":"Human papillomaviruses and non-melanoma skin cancer: Basic virology and clinical manifestations","volume":"23","author":"Nindl","year":"2007","journal-title":"Dis. Markers"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00030.2015","article-title":"Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease","volume":"96","author":"Chen","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/carcin\/bgi220","article-title":"Ultraviolet irradiation induces keratinocyte proliferation through the activation of epidermal growth factor receptor","volume":"27","author":"Putta","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wee, P., and Wang, Z. (2017). Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers, 9.","DOI":"10.3390\/cancers9050052"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.tcb.2013.11.002","article-title":"EGF receptor trafficking: Consequences for signalling and cancer","volume":"24","author":"Tomas","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000367959","article-title":"Dysregulation of epidermal growth factor receptor in actinic keratosis and squamous cell carcinoma","volume":"46","author":"Joseph","year":"2015","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41568-023-00583-5","article-title":"Advances in cutaneous squamous cell carcinoma","volume":"23","author":"Winge","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wang, Z., Wang, X., Shi, Y., Wu, S., Ding, Y., Yao, G., and Chen, J. (2024). Advancements in elucidating the pathogenesis of actinic keratosis: Present state and future prospects. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1330491"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12672-022-00510-4","article-title":"A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma","volume":"13","author":"Genenger","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41571-025-01058-2","article-title":"EMT and cancer: What clinicians should know","volume":"22","author":"Thompson","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"C1290","DOI":"10.1152\/ajpcell.00450.2021","article-title":"Metalloproteinases in dermal homeostasis","volume":"323","author":"Steinkamp","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1034\/j.1600-0625.2003.120201.x","article-title":"Matrix metalloproteinases in tumor progression: Focus on basal and squamous cell carcinomas","volume":"12","year":"2003","journal-title":"Exp. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1172\/JCI57415","article-title":"From keratinocyte to cancer: The pathogenesis and modeling of cutaneous squamous cell carcinoma","volume":"122","author":"Ratushny","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","article-title":"Matrix metalloproteinases: Regulators of the tumor microenvironment","volume":"141","author":"Kessenbrock","year":"2010","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of extracellular matrix remodelling in tumour progression and metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1186\/s12967-025-06447-w","article-title":"Matrix metalloproteinase-driven epithelial-mesenchymal transition: Implications in health and disease","volume":"23","author":"Radisky","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/modpathol.3800066","article-title":"Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas","volume":"17","author":"Fundyler","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/DAD.0b013e31824b1ddf","article-title":"Expression of gelatinases (MMP-2, MMP-9) and gelatinase activator (MMP-14) in actinic keratosis and in in situ and invasive squamous cell carcinoma","volume":"34","author":"Massaro","year":"2012","journal-title":"Am. J. Dermatopathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nri1418","article-title":"Matrix metalloproteinases as modulators of inflammation and innate immunity","volume":"4","author":"Parks","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tcb.2018.12.001","article-title":"EMT Transition States during Tumor Progression and Metastasis","volume":"29","author":"Pastushenko","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial\u2013mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Murata, M., Ito, T., Tanaka, Y., Yamamura, K., Furue, K., and Furue, M. (2020). Ovol2-mediated zeb1 downregulation may prevent promotion of actinic keratosis to cutaneous squamous cell carcinoma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030618"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial\u2013mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.cell.2008.12.043","article-title":"Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells","volume":"136","author":"Ezhkova","year":"2009","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1038\/onc.2008.333","article-title":"Repression of E-cadherin by the Polycomb group protein EZH2 in cancer","volume":"27","author":"Cao","year":"2008","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/DAD.0b013e318271292a","article-title":"Significance of cyclooxygenase 2, EZH-2 polycomb group and p53 expression in actinic keratosis and squamous cell carcinomas of the skin","volume":"35","author":"Athanassiadou","year":"2013","journal-title":"Am. J. Dermatopathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1684\/ejd.2013.2219","article-title":"Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis","volume":"24","author":"Xie","year":"2014","journal-title":"Eur. J. Dermatol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Valea, C.V., Klein, M., Hallermann, C., Schulze, H.J., Raguse, J.D., and Wermker, K. (2025). EZH2: An analysis of a potential new tumor marker in high-risk localization of cutaneous squamous cell carcinomas. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1438021"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1751-1097.2007.00261.x","article-title":"Cyclo-oxygenase-2 plays a critical role in UV-induced skin carcinogenesis","volume":"84","author":"Rundhaug","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrc2809","article-title":"Eicosanoids and cancer","volume":"10","author":"Wang","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_104","first-page":"232","article-title":"Molecular insights into proliferation and inflammation in actinic keratosis and photodynamic therapy: A comprehensive review of proliferation and inflammation markers","volume":"29","author":"Ceryn","year":"2025","journal-title":"Contemp. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.semcancer.2011.10.001","article-title":"Role of telomeres and telomerase in cancer","volume":"21","author":"Shay","year":"2011","journal-title":"Semin. Cancer Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.tibs.2013.07.001","article-title":"Telomerase: Central regulator of all of the hallmarks of cancer","volume":"38","author":"Low","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_107","first-page":"47","article-title":"Telomerase activity in melanoma and non-melanoma skin cancer","volume":"79","author":"Parris","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1038\/s41467-025-65687-y","article-title":"Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma","volume":"16","author":"Tandukar","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1158\/1541-7786.MCR-16-0003","article-title":"Understanding TERT promoter mutations: A common path to immortality","volume":"14","author":"Bell","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ventura, A., Pellegrini, C., Cardelli, L., Rocco, T., Ciciarelli, V., Peris, K., and Fargnoli, M.C. (2019). Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061333"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrc1838","article-title":"Modelling cancer in human skin tissue","volume":"6","author":"Khavari","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1158\/1078-0432.CCR-14-1768","article-title":"Mutational landscape of aggressive cutaneous squamous cell carcinoma","volume":"20","author":"Pickering","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/j.jid.2020.12.024","article-title":"The Genomic Landscape of Actinic Keratosis","volume":"141","author":"Thomson","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ccell.2016.04.004","article-title":"Squamous Cell Cancers: A Unified Perspective on Biology and Genetics","volume":"29","author":"Dotto","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev.cellbio.13.1.513","article-title":"Cellular functions regulated by Src family kinases","volume":"13","author":"Thomas","year":"1997","journal-title":"Ann. Rev. Cell Dev. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6036","DOI":"10.1074\/jbc.M406546200","article-title":"Srcasm modulates EGF and Src-kinase signaling in keratinocytes","volume":"280","author":"Li","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-0560.2007.00807.x","article-title":"Activation of Src-family tyrosine kinases in hyperproliferative epidermal disorders","volume":"35","author":"Ayli","year":"2008","journal-title":"J. Cutan. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.0303-6987.2005.320be.x","article-title":"Decreased Expression of Srcasm in Actinic Keratoses and Squamous Cell Carcinomas","volume":"32","author":"Dans","year":"2005","journal-title":"J. Cutan. Pathol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.4161\/cc.8.17.9514","article-title":"Skap associates with kinetochores and promotes the metaphase-to-anaphase transition","volume":"8","author":"Fang","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/ng.3091","article-title":"Recurrent point mutations in the kinetochore gene knstrn in cutaneous squamous cell carcinoma","volume":"46","author":"Lee","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1111\/jdv.15615","article-title":"Somatic mutations in kinetochore gene knstrn are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma","volume":"33","author":"Schmitz","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-Catenin Signaling, Disease, and Emerging Therapeutic Modalies","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/onc.2016.304","article-title":"Wnt signaling in cancer","volume":"36","author":"Zhan","year":"2017","journal-title":"Oncogene"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1111\/j.1365-2133.2005.06898.x","article-title":"Cyclin A and \u03b2-catenin expression in actinic keratosis, Bowen\u2019s disease and invasive squamous cell carcinoma of the skin","volume":"153","author":"Brasanac","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/\u03b2-Catenin Signaling and Disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1126\/science.1235122","article-title":"Cancer genome landscapes","volume":"339","author":"Vogelstein","year":"2013","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41467-018-03025-1","article-title":"Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin","volume":"9","author":"Bormann","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Herv\u00e1s-Mar\u00edn, D., Higgins, F., Sanmart\u00edn, O., L\u00f3pez-Guerrero, J.A., Ba\u00f1\u00f3, M.C., Igual, J.C., Quilis, I., and Sandoval, J. (2019). Genome-wide DNA methylation profiling identifies epigenetic alterations during cutaneous squamous cell carcinoma progression. PLoS ONE, 14.","DOI":"10.1101\/777227"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1111\/j.0022-202X.2004.22501.x","article-title":"p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma","volume":"122","author":"Brown","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/01.MP.0000089779.35435.9D","article-title":"E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions","volume":"16","author":"Chiles","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Meyer, T., Sand, M., Schmitz, L., and Stockfleth, E. (2021). The Role of Circular RNAs in Keratinocyte Carcinomas. Cancers, 13.","DOI":"10.3390\/cancers13164240"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jdermsci.2008.10.004","article-title":"MicroRNAs and the skin: Tiny players in the body\u2019s largest organ","volume":"53","author":"Sand","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/cdd.2013.125","article-title":"The miR-17\/92 cluster: A comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease","volume":"12","author":"Mogilyansky","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jdermsci.2017.01.012","article-title":"Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma","volume":"86","author":"Sand","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3892\/ol.2014.2066","article-title":"Inhibition of microRNA-21 upregulates the expression of programmed cell death 4 and phosphatase tensin homologue in the A431 squamous cell carcinoma cell line","volume":"8","author":"Li","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ccr.2011.10.014","article-title":"Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis","volume":"20","author":"Darido","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_137","first-page":"767","article-title":"Micro rna 31 and mmp-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin","volume":"314","author":"Carrato","year":"2022","journal-title":"Arch. Dermatol. Res."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Li, W.J., Wang, Y., Liu, R., Kasinski, A.L., Shen, H., Slack, F.J., and Tang, D.G. (2021). MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.640587"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1038\/emboj.2013.156","article-title":"A miR-34a-SIRT6 axis in the squamous cell differentiation network","volume":"32","author":"Lefort","year":"2013","journal-title":"EMBO J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nature06642","article-title":"A skin microRNA promotes differentiation by repressing \u2018stemness\u2019","volume":"452","author":"Yi","year":"2008","journal-title":"Nature"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/ncb1722","article-title":"The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1","volume":"10","author":"Gregory","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/bjd.15236","article-title":"MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma","volume":"177","author":"Valero","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Hosseini, T.M., Park, S.J., and Guo, T. (2024). The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review. Cancers, 16.","DOI":"10.3390\/cancers16162904"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Cozma, E.C., Banciu, L.M., Soare, C., and Cretoiu, S.M. (2023). Update on the Molecular Pathology of Cutaneous Squamous Cell Carcinoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076646"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e85270","DOI":"10.7554\/eLife.85270","article-title":"Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma","volume":"12","author":"Zou","year":"2023","journal-title":"eLife"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e360","DOI":"10.1002\/ski2.360","article-title":"MicroRNA expression profiling of cutaneous squamous cell carcinomas and precursor lesions","volume":"4","author":"Hossain","year":"2024","journal-title":"Skin Health Dis."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12195-025-00846-1","article-title":"High-Throughput Metabolomic Profiling of Skin Lesions: Comparative Study of Cutaneous Squamous Cell Carcinoma, Basal Cell Carcinoma, and Normal Skin Via e-Biopsy Sampling","volume":"18","author":"Louie","year":"2025","journal-title":"Cell Mol. Bioeng."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.2147\/IJGM.S357022","article-title":"Significant Biomarkers Identification Associated with Cutaneous Squamous Cell Carcinoma Progression","volume":"15","author":"Qiu","year":"2022","journal-title":"Int. J. Gen. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3221\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:16:09Z","timestamp":1791951369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":148,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cancers18193221"],"URL":"https:\/\/doi.org\/10.3390\/cancers18193221","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}