{"doi":"10.1016/j.jid.2019.12.028","title":"Phenotypic Plasticity of Cutaneous Squamous Cell Carcinoma Mediated by Cyclooxygenase-2","abstract":"Squamous cell carcinomas are the most common type of cancers that are capable of metastasis (Yan et al., 2011Yan W. Wistuba I.I. Emmert-Buck M.R. Erickson H.S. Squamous cell carcinoma - similarities and differences among anatomical sites.Am J Cancer Res. 2011; 1: 275-300Crossref PubMed Google Scholar). The enzymatic activity of cyclooxygenase-2 (Cox-2 also known as Ptgs2) contributes to the synthesis of prostanoids and is upregulated in several types of cancers, including cutaneous squamous cell carcinomas (cSCCs) (Hua et al., 2015Hua H.K. Jin C. Yang L.J. Tao S.Q. Zhu X.H. Expression of cyclooxygenase-2 in squamous cell carcinoma and keratoacanthoma and its clinical significance.Cell Biochem Biophys. 2015; 72: 475-480Crossref PubMed Scopus (4) Google Scholar, Sobolewski et al., 2010Sobolewski C. Cerella C. Dicato M. Ghibelli L. Diederich M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies.Int J Cell Biol. 2010; 2010: 215158Crossref PubMed Scopus (300) Google Scholar, Subbaramaiah and Dannenberg, 2003Subbaramaiah K. Dannenberg A.J. Cyclooxygenase 2: a molecular target for cancer prevention and treatment.Trends Pharmacol Sci. 2003; 24: 96-102Abstract Full Text Full Text PDF PubMed Scopus (586) Google Scholar; ). Cox-2 is an important regulator of tumor development and progression in the UV and chemical carcinogenesis models of cSCC (Elmets et al., 2014Elmets C.A. Ledet J.J. Athar M. Cyclooxygenases: mediators of UV-induced skin cancer and potential targets for prevention.J Invest Dermatol. 2014; 134: 2497-2502Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, Jiao et al., 2014aJiao J. Ishikawa T.O. Dumlao D.S. Norris P.C. Magyar C.E. Mikulec C. et al.Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.Mol Cancer Res. 2014; 12: 1677-1688Crossref PubMed Scopus (20) Google Scholar, Jiao et al., 2014bJiao J. Mikulec C. Ishikawa T.O. Magyar C. Dumlao D.S. Dennis E.A. et al.Cell-type-specific roles for COX-2 in UVB-induced skin cancer.Carcinogenesis. 2014; 35: 1310-1319Crossref PubMed Scopus (25) Google Scholar). In addition to tumorigenesis, Cox-2 may also have the potential to mediate the formation of a mesenchymal-like spindle cell form of cSCC as previous studies have also shown that Cox-2 can also regulate epithelial–mesenchymal transition (Bocca et al., 2014Bocca C. Ievolella M. Autelli R. Motta M. Mosso L. Torchio B. et al.Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness.Expert Opin Ther Targets. 2014; 18: 121-135Crossref PubMed Scopus (81) Google Scholar). Hair follicle stem cells (HFSCs) can act as the cancer cells-of-origin for cSCCs upon the expression of KrasG12D and loss of function in the tumor suppressor p53 (Lapouge et al., 2011Lapouge G. Youssef K.K. Vokaer B. Achouri Y. Michaux C. Sotiropoulou P.A. et al.Identifying the cellular origin of squamous skin tumors.Proc Natl Acad Sci USA. 2011; 108: 7431-7436Crossref PubMed Scopus (201) Google Scholar, White et al., 2011White A.C. Tran K. Khuu J. Dang C. Cui Y. Binder S.W. et al.Defining the origins of Ras/p53-mediated squamous cell carcinoma.Proc Natl Acad Sci USA. 2011; 108: 7425-7430Crossref PubMed Scopus (130) Google Scholar). Moreover, HFSC-originating cSCCs are primed to form mesenchymal-like cSCCs with morphological and gene expression characteristics of epithelial–mesenchymal transition in vivo (Figure 1a) (Latil et al., 2017Latil M. Nassar D. Beck B. Boumahdi S. Wang L. Brisebarre A. et al.Cell-type-specific chromatin states differentially prime squamous cell carcinoma tumor-initiating cells for epithelial to mesenchymal transition.Cell Stem Cell. 2017; 20: 191-204.e5Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, Pastushenko et al., 2018Pastushenko I. Brisebarre A. Sifrim A. Fioramonti M. Revenco T. Boumahdi S. et al.Identification of ","journal":"Journal of Investigative Dermatology","year":2020,"id":113218,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":534825,"name":"Dahihm Kim","orcid":"0000-0002-6153-1898","position":1,"is_corresponding":false},{"id":534826,"name":"Leanne R. 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