title: FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition.
abstract: Paclitaxel (Taxol) is currently used as the front-line chemotherapeutic drug for many types of human cancers. However, the emergence of drug resistance has been a major obstacle to the effective treatment of cancers in clinical settings. The transcription factor Forkhead box protein C2 (FOXC2) was recently demonstrated to activate the epithelial-mesenchymal transition (EMT). In this article, we present a novel role of FOXC2 in regulating chemoresistance of nasopharyngeal carcinoma (NPC) through the EMT. Using an EMT PCR array based on the screening of 84 genes, the expression of FOXC2 was notably upregulated in paclitaxel-resistant NPC cells (CNE2/t). We observed that the paclitaxel-resistant cells exhibited characteristic EMT phenotypes. The silencing of FOXC2 expression in the resistant cells can reverse the EMT molecular markers and chemoresistant phenotypes, such as cellular morphology, proliferation and anoikis. In an NPC xenograft mouse model, the downregulation of FOXC2 expression in the resistant NPC cells increased their sensitivity to paclitaxel treatment, resulting in reduced tumor growth. Taken together, our results suggest that FOXC2-mediated EMT may be an alternative mechanism through which cancer cells can initiate and maintain drug resistance. Thus, targeting FOXC2 may provide a novel strategy for overcoming chemoresistance in NPC therapy.
authors.affiliation: Department of Pathology, Xiangya Hospital and School of Basic Medical Sciences, Central South University, Changsha 410008, China.
authors.forename: Zhijiao
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Xie
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xiangpu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Nianhua
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiration, 2nd Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, 3(rd) Xiangya Hospital, Changsha 410008, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of Pathology, Xiangya Hospital and School of Basic Medical Sciences, Central South University, Changsha 410008, China. Electronic address: dyfeng743@126.com.
authors.forename: Deyun
authors.initials: D
authors.lastname: Feng
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: lunquansun@csu.edu.cn.
authors.forename: Lun-Quan
authors.initials: LQ
authors.lastname: Sun
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics; D002277:Carcinoma; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein; D017239:Paclitaxel
keywords: Chemoresistance; EMT; FOXC2; Nasopharyngeal carcinoma