Fas signaling promotes chemoresistance in gastrointestinal cancer by up-regulating P-glycoprotein

• DOI: 10.18632/oncotarget.2498
• Publication Date: 2015-09-15T23:37:14Z
• Authors: Haoxuan Zheng; Zhizhong Liu; Tao Liu; Yidong Cai; Yadong Wang; Shiyong Lin; Jinmin Chen; Jing Wang; Zhiqing Wang; Bo Jiang
• Keywords: Fas ligand

// Haoxuan Zheng 1, * , Zhizhong Liu 2, Tao Yidong Cai 3, Yadong Wang 1 Shiyong Lin 4 Jinmin Chen Jing Zhiqing Bo Jiang Guangdong Provincial Key Laboratory of Gastroenterology, Department Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 2 the Second People's Hospital Zhuhai, Zhuhai 519020, 3 Xiyuan Academy Chinese Sciences, Beijing 100091, Endoscopy and Laser, Sun Yat-sen University Cancer Center; State Oncology in South China; Collaborative Innovation Center for Medicine, 510060, These authors contributed equally to this work Correspondence to: Zheng, e-mail: [e-mail] Keywords: Fas signaling, epithelial-mesenchymal transition, chemoresistance, gastrointestinal cancer Received: July 09, 2014 Accepted: September 16, Published: October 15, ABSTRACT signaling promotes metastasis (GI) cells by inducing transition (EMT), EMT acquisition has been found cause chemoresistance. Here, we demonstrated that response chemotherapy GI patients with higher expression FasL was significantly worse than lower expression. Fas-induced activation ERK1/2-MAPK pathway decreased sensitivity chemotherapeutic agents promoted P-glycoprotein (P-gp). chemoresistance cell via upregulation P-gp increasing β-catenin decreasing miR-145. gene transcription binding promoter while miR-145 suppressed interacting mRNA 3'UTR P-gp. Immunostaining qRT-PCR analysis human samples revealed a positive association among FasL, β-catenin, P-gp, but negative correlation between or Altogether, our results showed could promote through modulation Our findings suggest signaling-based therapies should be administered cautiously, as may not only lead apoptosis also induce