{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:26:25Z","timestamp":1760059585325,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (F.C.T.)","doi-asserted-by":"publisher","award":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"]}]},{"name":"PThe Porto Comprehensive Cancer Center","award":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["U.I.D.B.\/00772\/2020","UID\/BIM\/04293\/2019","NORTE-01-0145-FEDER-072678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Thyroid tumors are common in humans and cats, occurring most commonly as benign lesions, whereas thyroid carcinoma is barely detected in both species. Determining the mutational status of MAPK-related genes (BRAF, NRAS, HRAS, and KRAS) and the activation status of MAPK and mTOR pathways is crucial for establishing the diagnosis, treatment, and prognosis of human patients. So far, the role of such players in feline thyroid tumorigenesis remains underexplored. This study aims to elucidate the presence and implications of potential shared molecular mechanisms between human and feline thyroid tumors. Fifteen formalin-fixed paraffin-embedded feline thyroid epithelial tumors (four tumors with atypia and 11 with no atypia) were collected to perform mutational and immunohistochemical analyses. Sanger sequencing targeting human homologous hotspots revealed no mutations in BRAF (human codon 600) or RAS (human codon 61) regions. A KRAS missense mutation (p.Gln232His) was identified in two tumors with no atypia of follicular pattern (2\/15, 13%). Regardless of the mutational status, pERK (Thr202\/Ty204) was immuno-expressed in 10\/11 (91%), pS6 (Ser235\/236) in 100%, and pAKT (Ser473) in 8\/11 (73%) of the tumors with no atypia. The expression patterns of pERK, pS6, and pAKT and their associations with clinical-pathological features seem to mirror the progression dynamics observed in human thyroid tumorigenesis. pAKT expression was associated with the presence of multiple tumor foci within the same thyroid lobe, suggesting its potential as a marker of aggressiveness in feline thyroid tumors. This study introduces cats as potential animal models for human thyroid tumorigenesis, with further research required to confirm such potential.<\/jats:p>","DOI":"10.3390\/vetsci12070617","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:43:15Z","timestamp":1750761795000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring MAPK and mTOR Pathways in Feline Thyroid Tumors"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-7394","authenticated-orcid":false,"given":"Alexandra","family":"Monteiro","sequence":"first","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biology and Environment, UTAD\u2014University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-7869","authenticated-orcid":false,"given":"Tiago Bordeira","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"CIVG\u2014Vasco da Gama Research Centre, Department of Veterinary Sciences, Vasco da Gama University School, 3020-210 Coimbra, Portugal"},{"name":"CEDIVET\u2014Laborat\u00f3rio Cl\u00ednico Veterin\u00e1rio, Le\u00e7a do Balio, 4465-671 Matosinhos, Portugal"}]},{"given":"In\u00eas","family":"Borges","sequence":"additional","affiliation":[{"name":"CEDIVET\u2014Laborat\u00f3rio Cl\u00ednico Veterin\u00e1rio, Le\u00e7a do Balio, 4465-671 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":false,"given":"Sule","family":"Canberk","sequence":"additional","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Mafalda","family":"Pinto","sequence":"additional","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-4560","authenticated-orcid":false,"given":"Isabel","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, UTAD\u2014University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CECAV\u2014Animal and Veterinary Research Centre, UTAD\u2014University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology, FMUP\u2014Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0140-2098","authenticated-orcid":false,"given":"Catarina","family":"Tavares","sequence":"additional","affiliation":[{"name":"Cancer Signalling & Metabolism, i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism, IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meuten, D.J. (2017). Tumors of the Endocrine Glands. Tumors in Domestic Animals, John Wiley & Sons, Inc.. [5th ed.].","DOI":"10.1002\/9781119181200"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/1098612X12464462","article-title":"Hyperthyroidism in cats: What\u2019s causing this epidemic of thyroid disease and can we prevent it?","volume":"14","author":"Peterson","year":"2012","journal-title":"J. Feline Med. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/1098612X15572416","article-title":"Prevalence and degree of thyroid pathology in hyperthyroid cats increases with disease duration: A cross-sectional analysis of 2096 cats referred for radioiodine therapy","volume":"18","author":"Peterson","year":"2016","journal-title":"J. Feline Med. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"key":"ref_5","first-page":"30","article-title":"Diagnosis and treatment of patients with thyroid cancer","volume":"8","author":"Nguyen","year":"2015","journal-title":"Am. Health Drug Benefits"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ecl.2007.04.009","article-title":"Thyroid nodules: Clinical importance, assessment, and treatment","volume":"36","author":"Gharib","year":"2007","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1089\/thy.1998.8.989","article-title":"Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules","volume":"8","author":"Hagag","year":"1998","journal-title":"Thyroid"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"T97","DOI":"10.1530\/JOE-14-0461","article-title":"Animal models of disease: Feline hyperthyroidism: An animal model for toxic nodular goiter","volume":"223","author":"Peterson","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1677\/joe.1.06277","article-title":"Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: Parallels with human hyperthyroidism","volume":"186","author":"Watson","year":"2005","journal-title":"J. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/105072502320288410","article-title":"Feline thyroid adenomas are in part associated with mutations in the G(s alpha) gene and not with polymorphisms found in the thyrotropin receptor","volume":"12","author":"Peeters","year":"2002","journal-title":"Thyroid"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Giuliano, A. (2021). Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma. Biology, 11.","DOI":"10.3390\/biology11010054"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3390\/vetsci2030111","article-title":"Cats, Cancer and Comparative Oncology","volume":"2","author":"Cannon","year":"2015","journal-title":"Vet. Sci."},{"key":"ref_13","first-page":"85","article-title":"Diagnosis and management of feline hyperthyroidism: Current perspectives","volume":"5","author":"Vaske","year":"2014","journal-title":"Vet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1532-950X.2006.00146.x","article-title":"Results of thyroidectomy in 101 cats with hyperthyroidism","volume":"35","author":"Naan","year":"2006","journal-title":"Vet. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0195-5616(02)00023-2","article-title":"Feline thyroid surgery","volume":"32","author":"Padgett","year":"2002","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.3390\/ijms13021886","article-title":"The mTOR signalling pathway in human cancer","volume":"13","author":"Lopes","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/1947601911408079","article-title":"RAS Interaction with PI3K: More Than Just Another Effector Pathway","volume":"2","author":"Castellano","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/1947601911411084","article-title":"Ras in cancer and developmental diseases","volume":"2","author":"Santos","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R117","DOI":"10.1530\/EJE-15-0605","article-title":"ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome","volume":"174","author":"Tavares","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrc3431","article-title":"Molecular pathogenesis and mechanisms of thyroid cancer","volume":"13","author":"Xing","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1354\/vp.36-2-117","article-title":"Overexpression of c-Ras in hyperplasia and adenomas of the feline thyroid gland: An immunohistochemical analysis of 34 cases","volume":"36","author":"Merryman","year":"1999","journal-title":"Vet. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pinello, K., Pires, I., Castro, A.F., Carvalho, P.T., Santos, A., de Matos, A., Queiroga, F., and Niza-Ribeiro, J. (2022). Vet-OncoNet: Developing a Network of Veterinary Oncology and Reporting a Pioneering Portuguese Experience. Vet. Sci., 9.","DOI":"10.3390\/vetsci9020072"},{"key":"ref_23","unstructured":"Kiupel, M. (2008). Histological Classification of Tumors of the Endocrine System of Domestic Animals, Armed Forces Institute of Pathology in Cooperation with the CL Davis DVM Foundation and the World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology. [2nd ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Povoa, A.A., Teixeira, E., Bella-Cueto, M.R., Batista, R., Pestana, A., Melo, M., Alves, T., Pinto, M., Sobrinho-Simoes, M., and Maciel, J. (2021). Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13092048"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Matos, M.L., Pinto, M., Alves, M., Canberk, S., Goncalves, A., Bugalho, M.J., Papoila, A.L., and Soares, P. (2024). Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas. Diagnostics, 14.","DOI":"10.3390\/diagnostics14030278"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: A new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D933","DOI":"10.1093\/nar\/gkac958","article-title":"Ensembl 2023","volume":"51","author":"Martin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS Recommendations for the Description of Sequence Variants: 2016 Update","volume":"37","author":"Dalgleish","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btab051","article-title":"Mutalyzer 2: Next generation HGVS nomenclature checker","volume":"37","author":"Lefter","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tavares, C., Eloy, C., Melo, M., Gaspar da Rocha, A., Pestana, A., Batista, R., Bueno Ferreira, L., Rios, E., Sobrinho Simoes, M., and Soares, P. (2018). mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051448"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.surg.2016.06.050","article-title":"pmTOR is a marker of aggressiveness in papillary thyroid carcinomas","volume":"160","author":"Tavares","year":"2016","journal-title":"Surgery"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/07435800.2012.723292","article-title":"ERK phosphorylation is not increased in papillary thyroid carcinomas with BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues","volume":"38","author":"Kim","year":"2013","journal-title":"Endocr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Asproni, P., Millanta, F., Ressel, L., Podesta, F., Parisi, F., Vannozzi, I., and Poli, A. (2021). An Immunohistochemical Study of the PTEN\/AKT Pathway Involvement in Canine and Feline Mammary Tumors. Animals, 11.","DOI":"10.3390\/ani11020365"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23065","DOI":"10.1074\/jbc.M200328200","article-title":"c-Raf\/MEK\/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells","volume":"277","author":"Iijima","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tvjl.2010.12.016","article-title":"Activation of AKT in feline mammary carcinoma: A new prognostic factor for feline mammary tumours","volume":"191","author":"Maniscalco","year":"2012","journal-title":"Vet. J."},{"key":"ref_40","unstructured":"Feldman, E.C., Nelson, R.W., Reusch, C.E., and Scott-Moncrieff, J.C. (2015). The Thyroid gland. Canine and Feline Endocrinology, Elsevier Saunders. [4th ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.cvsm.2007.03.008","article-title":"Thyroid tumors in dogs and cats","volume":"37","author":"Barber","year":"2007","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Pinello, K., Amorim, I., Pires, I., Canadas-Sousa, A., Catarino, J., Faisca, P., Branco, S., Peleteiro, M.C., Silva, D., and Severo, M. (2022). Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats. Vet. Sci., 9.","DOI":"10.3390\/vetsci9100535"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jcpa.2021.01.013","article-title":"Pathological and Immunohistochemical Characterization of Thyroid Neoplasms in Cats","volume":"184","author":"Argenta","year":"2021","journal-title":"J. Comp. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/CCO.0000000000001012","article-title":"Pathology and new insights in thyroid neoplasms in the 2022 WHO classification","volume":"36","author":"Lebrun","year":"2024","journal-title":"Curr. Opin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jcpa.2020.04.002","article-title":"Histopathological and Immunohistochemical Characteristics of Thyroid Carcinoma in the Dog","volume":"177","author":"Soares","year":"2020","journal-title":"J. Comp. Pathol."},{"key":"ref_46","unstructured":"Lloyd, R.V., Osamura, R.Y., Kl\u00f6ppel, G., and Rosai, J. (2017). WHO Classification of Tumours of Endocrine Organs, World Health Organization (IARC). [4th ed.]."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Derwich, A., Sykutera, M., Brominska, B., Andrusiewicz, M., Ruchala, M., and Sawicka-Gutaj, N. (2023). Clinical Implications of mTOR Expression in Papillary Thyroid Cancer-A Systematic Review. Cancers, 15.","DOI":"10.3390\/cancers15061665"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1677\/erc.1.0978","article-title":"BRAF mutation in thyroid cancer","volume":"12","author":"Xing","year":"2005","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jfms.2008.02.010","article-title":"Feline thyroid carcinoma: Diagnosis and response to high-dose radioactive iodine treatment","volume":"11","author":"Hibbert","year":"2009","journal-title":"J. Feline Med. Surg."},{"key":"ref_50","unstructured":"Peterson, M.E. (2011, January 15\u201319). Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 ACVIM Forum, Denver, CO, USA."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1136\/vr.153.15.468","article-title":"K-ras protooncogene mutations in feline pancreatic adenocarcinomas","volume":"153","author":"Mayer","year":"2003","journal-title":"Vet. Rec."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1177\/0300985820974279","article-title":"Histological Classification and Immunohistochemical Study of Feline Colorectal Epithelial Tumors","volume":"58","author":"Uneyama","year":"2021","journal-title":"Vet. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1136\/jmg.2003.015339","article-title":"Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer","volume":"41","author":"Vasko","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.yexmp.2017.11.009","article-title":"AKT activity is elevated in aggressive thyroid neoplasms where it promotes proliferation and invasion","volume":"103","author":"Matson","year":"2017","journal-title":"Exp. Mol. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.trsl.2014.06.005","article-title":"Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to chemosensitize anaplastic thyroid carcinoma","volume":"164","author":"Milosevic","year":"2014","journal-title":"Transl. Res."},{"key":"ref_56","first-page":"675-e180","article-title":"Persistent activation of the mammalian target of rapamycin signalling pathway in cutaneous squamous cell carcinomas in cats","volume":"32","author":"Massone","year":"2021","journal-title":"Vet. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3109\/07853890.2014.912836","article-title":"PI3K\/AKT signaling pathway and cancer: An updated review","volume":"46","author":"Martini","year":"2014","journal-title":"Ann. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation","volume":"36","author":"Mendoza","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1210\/jc.2008-0273","article-title":"Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase\/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers","volume":"93","author":"Liu","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1067\/msy.2001.118381a","article-title":"p44\/p42-MAP kinase expression in papillary thyroid carcinomas","volume":"130","author":"Specht","year":"2001","journal-title":"Surgery"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8002","DOI":"10.1158\/0008-5472.CAN-07-2471","article-title":"Thyroid-stimulating hormone initiated proliferative signals converge in vivo on the mTOR kinase without activating AKT","volume":"67","author":"Brewer","year":"2007","journal-title":"Cancer Res."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/7\/617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:57:53Z","timestamp":1760032673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/7\/617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["vetsci12070617"],"URL":"https:\/\/doi.org\/10.3390\/vetsci12070617","relation":{},"ISSN":["2306-7381"],"issn-type":[{"type":"electronic","value":"2306-7381"}],"subject":[],"published":{"date-parts":[[2025,6,24]]}}}