Open AccessTwist1 confers multidrug resistance in colon cancer through upregulation of ATP-binding cassette transporters
Author(s) -
Yanrong Liu,
Lan Liang,
Jian Zhao,
Yang Zhang,
Min Zhang,
Weilong Zhong,
Qiang Zhang,
Junjie Wei,
Meng Li,
Jie Yuan,
Shuang Chen,
Shumin Zong,
Huijuan Liu,
Jing Meng,
Yuan Qin,
Bo Sun,
Lan Yang,
Honggang Zhou,
Tao Sun,
Cheng Yang
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.17548
Subject(s) - medicine , multiple drug resistance , drug resistance , cancer , epithelial–mesenchymal transition , atp binding cassette transporter , cancer research , oncology , transporter , metastasis , biology , genetics , gene
Multidrug resistance is a major problem in colon cancer treatment. However, its molecular mechanisms remain unclear. Recently, the epithelial-mesenchymal transition (EMT) in anticancer drug resistance has attracted increasing attention. This study investigated whether vincristine treatment induces EMT and promotes multidrug resistance in colon cancer. The result showed that vincristine treatment increases the expression of several ATP-binding cassette transporters in invasive human colon adenocarcinoma cell line (HCT-8). Vincristine-resistant HCT-8 cells (HCT-8/V) acquire a mesenchymal phenotype, and thus its migratory and invasive ability are increased both in vitro and in vivo . The master transcriptional factors of EMT, especially Twist1, were significantly increased in the HCT-8/V cell line. Moreover, the ectopic expression of Twist1 increased the chemoresistance of HCT-8 cells to vincristine and increased the expression levels and promoter activities of ABCB1 and ABCC1. Furthermore, Twist1 silencing reverses the EMT phenotype, enhances the chemosensitivity of HCT-8/ V cells to anticancer agents in vitro and in vivo , and downregulates the expression of ABCB1 and ABCC1. Twist1-mediated promotion of ABCB1 and ABCC1 expression levels plays an important role in the drug resistance of colon cancer cells.