{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:48:17Z","timestamp":1760147297458,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/ CVT\/00772\/2020","LA\/P\/0059\/2020"],"award-info":[{"award-number":["UIDB\/ CVT\/00772\/2020","LA\/P\/0059\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/ CVT\/00772\/2020","LA\/P\/0059\/2020"],"award-info":[{"award-number":["UIDB\/ CVT\/00772\/2020","LA\/P\/0059\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>C-terminal tensin-like (tensin-4\/TNS4\/CTEN) is the fourth member of the tensin family, frequently described as displaying oncological functions, including cellular migration, invasion, adhesion, growth, metastasis, epithelial to mesenchymal transition, and apoptosis, in several different types of cancer. To investigate, for the first time, the clinical significance of CTEN in squamous cell carcinoma (SCC) of dogs, we studied a total of 45 SCC sections from various dog breeds. The mean age of the affected dogs was 8.9 \u00b1 3.6 years. Immunohistochemistry confirmed strong cytoplasmatic CTEN expression in the basal layer of the epidermis next to the tumor. We detected high CTEN expression associated with the highest grade of the tumor (grade III) and observed 100% of immunopositivity for this tumor grading (p &lt; 0.0001). These data suggest that CTEN is an oncogene in SCC of dogs and a promising biomarker and a therapeutic target for dogs affected by SCC.<\/jats:p>","DOI":"10.3390\/vetsci10020086","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:22:16Z","timestamp":1674620536000},"page":"86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemical Expression of Tensin-4\/CTEN in Squamous Cell Carcinoma in Dogs"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-7394","authenticated-orcid":false,"given":"Alexandra","family":"Monteiro","sequence":"first","affiliation":[{"name":"Department of Biology and Environment, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (i3S), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-0240","authenticated-orcid":false,"given":"Leonor","family":"Delgado","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences-CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Pathology Department, INNO Servi\u00e7os Especializados em Veterin\u00e1ria, 4710-503 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-1297","authenticated-orcid":false,"given":"Lu\u00eds","family":"Monteiro","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences-CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Pathology Department, INNO Servi\u00e7os Especializados em Veterin\u00e1ria, 4710-503 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-4560","authenticated-orcid":false,"given":"Isabel","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CECAV-Veterinary and Animal Research Center, University of Tr\u00e1s-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-5374","authenticated-orcid":false,"given":"Justina","family":"Prada","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CECAV-Veterinary and Animal Research Center, University of Tr\u00e1s-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal"}]},{"given":"Teresa","family":"Raposo","sequence":"additional","affiliation":[{"name":"Horizon Discovery, Cambridge CB25 9TL, UK"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","first-page":"4217","article-title":"Cten, a COOH-Terminal Tensin-Like Protein with Prostate Restricted Expression, is Down-Regulated in Prostate Cancer","volume":"62","author":"Lo","year":"2002","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1357-2725(03)00171-7","article-title":"Tensin","volume":"36","author":"Lo","year":"2004","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/boc.201600053","article-title":"Tensins are versatile regulators of Rho GTPase signalling and cell adhesion","volume":"109","author":"Blangy","year":"2017","journal-title":"Biol Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R331","DOI":"10.1016\/j.cub.2017.02.041","article-title":"Tensins","volume":"27","author":"Lo","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nizio\u0142, M., and Pryczynicz, A. (2022, January 31). The role of tensins in malignant neoplasms. Archives of Medical Science, 2021. Available online: https:\/\/www.archivesofmedicalscience.com\/The-role-of-tensins-in-malignant-neoplasms,127085,0,2.html.","DOI":"10.5114\/aoms\/127085"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1073\/pnas.262791999","article-title":"Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling","volume":"100","author":"Calderwood","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.bbamcr.2018.10.008","article-title":"Identification of subcellular targeting sequences of Cten reveals its role in cell proliferation","volume":"1866","author":"Hong","year":"2019","journal-title":"Biochim. Biophys. Acta. Mol. Cell. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4563","DOI":"10.1158\/0008-5472.CAN-09-0117","article-title":"Up-regulation of C-terminal tensin-like molecule promotes the tumorigenicity of colon cancer through beta-catenin","volume":"69","author":"Liao","year":"2009","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1038\/onc.2011.26","article-title":"Cten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer","volume":"30","author":"Albasri","year":"2011","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10549-010-0890-3","article-title":"CTEN (C-terminal tensin-like), a novel oncogene overexpressed in invasive breast carcinoma of poor prognosis","volume":"126","author":"Albasri","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/iep.12300","article-title":"TGFbeta1-induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer","volume":"99","author":"Asiri","year":"2018","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/pin.12811","article-title":"Cten promotes Epithelial-Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src","volume":"69","author":"Asiri","year":"2019","journal-title":"Pathol. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jtcvs.2014.08.087","article-title":"C-terminal tensin-like protein mediates invasion of human lung cancer cells and is regulated by signal transducer and activator of transcription 3","volume":"149","author":"Bennett","year":"2015","journal-title":"J. Thorac. Cardiovas. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fleming, J.C., Woo, J.M., Moutasim, K., Hanley, C.J., Frampton, S.J., Wood, O., Ward, M., Woelk, C.H., Ottensmeier, C.H., and Hafizi, S. (2020). CTEN Induces Tumour Cell Invasion and Survival and Is Prognostic in Radiotherapy-Treated Head and Neck Cancer. Cancers, 12.","DOI":"10.3390\/cancers12102963"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/ncb1622","article-title":"A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration","volume":"9","author":"Katz","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.devcel.2014.03.024","article-title":"Tensin-4-dependent MET stabilization is essential for survival and proliferation in carcinoma cells","volume":"29","author":"Muharram","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1002\/mc.22704","article-title":"Cten promotes epithelial-mesenchymal transition through the post-transcriptional stabilization of Snail","volume":"56","author":"Thorpe","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000076141","article-title":"Cten mRNA expression is correlated with tumor progression in thymoma","volume":"24","author":"Sasaki","year":"2003","journal-title":"Tumour Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sjoestroem, C., Khosravi, S., Zhang, G.H., Martinka, M., and Li, G. (2013). C-terminal tensin-like protein is a novel prognostic marker for primary melanoma patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080492"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20964","DOI":"10.18632\/oncotarget.4122","article-title":"Tensin4 is up-regulated by EGF-induced ERK1\/2 activity and promotes cell proliferation and migration in hepatocellular carcinoma","volume":"6","author":"Chan","year":"2015","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al-Ghamdi, S., Albasri, A., Cachat, J., Ibrahem, S., Muhammad, B.A., Jackson, D., Nateri, A.S., Kindle, K.B., and Ilyas, M. (2011). Cten is targeted by Kras signalling to regulate cell motility in the colon and pancreas. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020919"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MPA.0b013e3182557ceb","article-title":"C-terminal tensin-like gene functions as an oncogene and promotes cell motility in pancreatic cancer","volume":"42","author":"Cachat","year":"2013","journal-title":"Pancreas"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1245\/s10434-008-9989-8","article-title":"Prognostic relevance of Tensin4 expression in human gastric cancer","volume":"15","author":"Sakashita","year":"2008","journal-title":"Ann Surg Oncol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19799","DOI":"10.1073\/pnas.1911865116","article-title":"Force-induced recruitment of cten along keratin network in epithelial cells","volume":"116","author":"Cheah","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cub.2010.12.037","article-title":"Transcriptional profiling identifies TNS4 function in epithelial tubulogenesis","volume":"21","author":"Kwon","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0190-9622(92)70001-V","article-title":"Biology of cutaneous squamous cell carcinoma","volume":"26","author":"Kwa","year":"1992","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1365-2133.2009.09458.x","article-title":"UV-induced squamous cell carcinoma\u2014A role for antiapoptotic signalling pathways","volume":"161","author":"Rodust","year":"2009","journal-title":"Br J Dermatol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1177\/0300985813490757","article-title":"Digital squamous cell carcinoma in dogs: Epidemiological, histological, and immunohistochemical study","volume":"50","author":"Belluco","year":"2013","journal-title":"Vet. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1354\/vp.40-3-332","article-title":"Squamous cell carcinoma of the anal sac in five dogs","volume":"40","author":"Esplin","year":"2003","journal-title":"Vet. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/00000372-198404000-00017","article-title":"Basal- and squamous-cell neoplasms of dogs and cats","volume":"6","author":"Goldschmidt","year":"1984","journal-title":"Am. J. Dermatopathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jcpa.2016.05.011","article-title":"Swiss Canine Cancer Registry 1955-2008: Occurrence of the Most Common Tumour Diagnoses and Influence of Age, Breed, Body Size, Sex and Neutering Status on Tumour Development","volume":"155","author":"Gruntzig","year":"2016","journal-title":"J. Comp. Pathol."},{"key":"ref_32","unstructured":"Meuten, D.J. (2017). Epithelial and Melanocytic Tumors of the Skin, in Tumors in Domestic Animals, John Wiley & Sons, Inc., North Carolina State University Raleigh."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Meuten, D.J. (2002). Tumors of the Skin and Soft Tissues, in Tumors in Domestic Animals, Iowa State Press.","DOI":"10.1002\/9780470376928"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1186\/s13054-019-2659-3","article-title":"Translational medicine between human and veterinary emergency and critical care medicine: a story meant to have a happy ending","volume":"23","author":"Felix","year":"2019","journal-title":"Crit. Care"},{"key":"ref_36","unstructured":"Goldschmidt, M.H., Munday, J.S., Scruggs, J.L., Klopfleisc, R., and Kiuppel, M. (2018). Surgical Pathology of Tumors of Domestic Animals; Davis-Thompson DVM Foundation, Davis-Thompson DVM Foundation."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4103\/0973-029X.84485","article-title":"A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis","volume":"15","author":"Akhter","year":"2011","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.jid.2016.10.039","article-title":"Integrin-beta4-TNS4-Focal Adhesion Kinase Signaling Mediates Keratinocyte Proliferation in Human Skin","volume":"137","author":"Seo","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","unstructured":"Nomenclature, I.C.o.V.G.A (2017). Nomina Anatomica Veterinaria (Veterinary Anatomical Names), Editorial Committee WAVA. [6th ed]."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"960","DOI":"10.2460\/javma.239.7.960","article-title":"Identification of the most common cutaneous neoplasms in dogs and evaluation of breed and age distributions for selected neoplasms","volume":"239","author":"Villamil","year":"2011","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1751-0813.1987.tb09673.x","article-title":"Skin neoplasms of dogs in Sydney","volume":"64","author":"Rothwell","year":"1987","journal-title":"Aust. Vet. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"84112","DOI":"10.18632\/oncotarget.21109","article-title":"Overexpression of CTEN relates to tumor malignant potential and poor outcomes of adenocarcinoma of the esophagogastric junction","volume":"8","author":"Aratani","year":"2017","journal-title":"Oncotarget"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0169-5002(03)00037-0","article-title":"Cten mRNA expression was correlated with tumor progression in lung cancers","volume":"40","author":"Sasaki","year":"2003","journal-title":"Lung Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.2353\/ajpath.2009.080545","article-title":"Epithelial-mesenchymal transition: a cancer researcher\u2019s conceptual friend and foe","volume":"174","author":"Klymkowsky","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Loh, C.Y., Chai, J.Y., Tang, T.F., Wong, W.F., Sethi, G., Shanmugam, M.K., Chong, P.P., and Looi, C.Y. (2019). The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells, 8.","DOI":"10.3390\/cells8101118"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/path.2508","article-title":"C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer","volume":"218","author":"Albasri","year":"2009","journal-title":"J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1177\/0300985817707005","article-title":"Invasive Front Grading and Epithelial-Mesenchymal Transition in Canine Oral and Cutaneous Squamous Cell Carcinomas","volume":"54","author":"Nagamine","year":"2017","journal-title":"Vet. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1083\/jcb.200608015","article-title":"The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1","volume":"176","author":"Liao","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_49","first-page":"6581","article-title":"DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1","volume":"60","author":"Ng","year":"2000","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kwiecinski, M., Noetel, A., Elfimova, N., Trebicka, J., Schievenbusch, S., Strack, I., Molnar, L., von Brandenstein, M., T\u00f6x, U., and Nischt, R. (2011). Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells by miRNA-29 induction. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024568"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2000031","DOI":"10.1002\/adbi.202000031","article-title":"Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion","volume":"4","author":"Raposo","year":"2020","journal-title":"Adv. Biosyst."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, D., Xiong, H., Ellis, A.E., Northrup, N.C., Dobbin, K.K., Shin, D.M., and Zhao, S.Y. (2015). Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005277"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tvjl.2018.12.024","article-title":"Immunohistochemical expression of selected phosphoproteins of the mTOR signalling pathway in canine cutaneous squamous cell carcinoma","volume":"245","author":"Massone","year":"2019","journal-title":"Vet. J."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Delgado, L., Brilhante-Sim\u00f5es, P., Garcez, F., Monteiro, L., Pires, I., and Prada, J. (2022). p-S6 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma. Biomolecules, 12.","DOI":"10.3390\/biom12070935"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/10\/2\/86\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:46Z","timestamp":1760120086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/10\/2\/86"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,24]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["vetsci10020086"],"URL":"https:\/\/doi.org\/10.3390\/vetsci10020086","relation":{},"ISSN":["2306-7381"],"issn-type":[{"type":"electronic","value":"2306-7381"}],"subject":[],"published":{"date-parts":[[2023,1,24]]}}}