The 14-3-3σ/GSK3β/β-catenin/ZEB1 regulatory loop modulates chemo-sensitivity in human tongue cancer

作者：Cong Peng, Xiaoting Jia, Yan Xiong, Jiang Yin, Nan Li, Yingen Deng, Kai Luo, Qiong Zhang, Chengkun Wang, Zhijie Zhang, Guopei Zheng, Zhimin He · 发表于：Oncotarget · 年份：2015 · DOI：10.18632/oncotarget.3896 · 被引用次数：16 · 研究领域：14-3-3 protein interactions、Ubiquitin and proteasome pathways、Protein Tyrosine Phosphatases

// Cong Peng 1, * , Xiaoting Jia 1, * , Yan Xiong 2 , Jiang Yin 1 , Nan Li 1 , Yingen Deng 1 , Kai Luo 1 , Qiong Zhang 1 , Chengkun Wang 1 , Zhijie Zhang 1 , Guopei Zheng 1 , Zhimin He 1 1 Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China 2 Department of Pharmacology, Guangzhou Institute of Snake Venom Research, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, Guangdong, China * These authors have contributed equally to this work Correspondence to: Guopei Zheng, e-mail: zhengguopei@126.com Zhimin He, e-mail: hezhimin2005@yahoo.com Keywords: tongue cancer, 14-3-3σ, GSK3β, β-catenin, chemosensitivity Received: March 10, 2015      Accepted: April 25, 2015      Published: May 08, 2015 ABSTRACT Here we demonstrated that chemotherapy induced 14-3-3σ expression in tongue cancer (TC) cells and overexpressed 14-3-3σ sensitized TC cells to chemotherapy especially in multidrug resistant TC (MDR-TC) cells. In agreement, 14-3-3σ knockdown enhanced resistance of TC cells to chemotherapy. Mechanically, we found 14-3-3σ physically bound to GSK3β in protein level and the binding inhibited β-catenin signaling. Coincidentally, chemotherapy as well as 14-3-3σ overexpression led to increase of GSK3β protein level. Increased GSK3β protein sensitized TC cells to chemotherapy. Moreover, de...