title: BEX3 contributes to cisplatin chemoresistance in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) can develop cisplatin-resistant phenotype. Research has revealed that enriched in cancer stem cell population is involved in developing cisplatin-resistant phenotype. CD271 is a candidate stem cell maker in head and neck cancers. The CD receptor does not possess any enzymatic property. Signal transduction function of CD271 is mediated by the cellular receptor-associated protein. Our data showed that Brain-expressed X-linked 3 (BEX3), a CD271 receptor-associated protein, was overexpressed in NPC. BEX3 overexpression was a unique event in cancer developed in the head and neck regions, especially NPC. BEX3 expression was inducible by cisplatin in NPC. In cisplatin-resistant NPC xenograft, treatment with nontoxic level of cisplatin led to a remarkable increase in BEX3 level. High BEX3 expression was accompanied with high octamer-binding transcription factor 4 (OCT4) expression in cisplatin-resistant NPC. To confirm the inducing role of BEX3 on OCT4 expression, we knockdown BEX3 using siRNA and compared the expression of OCT4 with mock transfectants. Suppressing BEX3 transcripts led to a significant reduction in OCT4. In addition, targeting BEX3 using shRNA could increase the sensitivity of NPC cells to cisplatin. In summary, our results indicated a unique functional role of BEX3 in mediating the sensitivity of NPC cells to cisplatin. Targeting or blocking BEX3 activity might be useful in reversing the cisplatin-resistant phenotype in NPC.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.|Department of Otolaryngology, The First People's Hospital of Foshan, Guangdong Province, China.
authors.forename: John Zeng-Hong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Chen
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Chu
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jimmy Yu-Wai
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Thian-Sze
authors.initials: TS
authors.lastname: Wong
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C410727:BEX3 protein, human; C485842:Ngfrap1 protein, mouse; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D002945:Cisplatin
keywords: Acquired resistance; BEX3; OCT4; cisplatin; nasopharyngeal carcinoma