The AKT/GSK3 β mediated Slug expression contributes to oxaliplatin resistance in 4 colorectal cancer via up-regulation of ERCC1.

The AKT/GSK3β mediated Slug expression contributes to oxaliplatin resistance in 4 colorectal cancer via up-regulation of ERCC1. Oncol Res. 2020 Apr 24;: Authors: Wei W, Ma XD, Jiang GM, Shi B, Zhong W, Sun CL, Zhao L, Hou YJ, Wang H Abstract Although oxaliplatin serves as one of the first-line drugs prescribed for treating26 colorectal cancer (CRC), the therapeutic effect is disappointing due to drug resistance.27 So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In28 this study, we found the chemo-resistance in oxaliplatin-resistant HCT116 cells29 (HCT116/OXA) was mediated by the up-regulation of ERCC1 expression. Besides, the30 acquisition of resistance induced epithelial-mesenchymal transition (EMT), as well as31 the Slug over-expression. On the contrary, Slug silencing reversed EMT phenotype,32 decreased ERCC1 expression, and ameliorate the drug resistance. Further mechanistical33 studies revealed the enhanced Slug expression was resulted from the activation of34 AKT/GSK3β signaling. Moreover, in CRC patients, co-expression of Slug and ERCC135 was observed, and increased Slug expression was significantly correlated with36 clinicopathological factors and prognosis. Taken together, the simultaneous inhibition of37 AKT/GSK3β/Slug axis may be of significance for surmounting metastasis and38 chemo-resistance, thereby improving the therapeutic outcome of oxaliplatin. PMID: 32331534 [PubMed - a...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research