@Article{096504020X15877284857868,
AUTHOR = {Wei Wei, Xiao-Dong Ma, Guan-Min Jiang, Bin Shi, Wen Zhong, Chun-Lei Sun, Liang Zhao, Yan-Jiao Hou, Hao Wang},
TITLE = {The AKT/GSK3β-Mediated Slug Expression Contributes to Oxaliplatin  Resistance in Colorectal Cancer via Upregulation of ERCC1},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {4},
PAGES = {423--438},
URL = {http://www.techscience.com/or/v28n4/48524},
ISSN = {1555-3906},
ABSTRACT = {Although oxaliplatin serves as one of the first-line drugs prescribed for treating colorectal cancer (CRC), the 
therapeutic effect is disappointing due to drug resistance. So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In this study, we found the chemoresistance in oxaliplatin-resistant HCT116 cells 
(HCT116/OXA) was mediated by the upregulation of ERCC1 expression. In addition, the acquisition of resistance induced epithelial–mesenchymal transition (EMT) as well as the Slug overexpression. On the contrary, 
Slug silencing reversed the EMT phenotype, decreased ERCC1 expression, and ameliorated drug resistance. 
Further mechanistical studies revealed the enhanced Slug expression resulted from the activation of AKT/
glycogen synthase kinase 3 (GSK3 ) signaling. Moreover, in CRC patients, coexpression of Slug and ERCC1 
was observed, and increased Slug expression was significantly correlated with clinicopathological factors and 
prognosis. Taken together, the simultaneous inhibition of the AKT/GSK3 /Slug axis may be of significance for 
surmounting metastasis and chemoresistance, thereby improving the therapeutic outcome of oxaliplatin.},
DOI = {10.3727/096504020X15877284857868}
}