FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition. Issue 2 (28th July 2015)

• Record Type: Journal Article
• Authors: Zhou, Zhijiao; Zhang, Lu; Xie, Bowen; Wang, Xiangpu; Yang, Xinhui; Ding, Nianhua; Zhang, Jing; Liu, Qingqing; Tan, Guolin; Feng, Deyun; Sun, Lun-Quan
• Is Part Of: Cancer letters. Volume 363:Issue 2(2015)
• Page Start: 137
• Page End: 145
• Publication Date: 2015-07-28
• Subjects: Chemoresistance -- FOXC2 -- EMT -- Nasopharyngeal carcinoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.04.008
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: FOXC2 plays a novel role in regulating chemoresistance of nasopharyngeal carcinoma (NPC). FOXC2-mediated EMT may be an important mechanism through which cancer cells acquire and maintain drug resistance. FOXC2 expression is critical for both EMT properties and resistance to cell death (such as anoikis) in NPC cells. 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.