Targeting hexokinase 2 increases the sensitivity of oxaliplatin by Twist1 in colorectal cancer.
Targeting hexokinase 2 increases the sensitivity of oxaliplatin by Twist1 in colorectal cancer.
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靶向己糖酶2可提高扭结癌中扭曲1的奥沙利铂的敏感性。
DOI：
10.1111/jcmm.16842
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发表时间：
2021-09
影响因子：
5.3
通讯作者：
Zhang XD
中科院分区：
文献类型：
--
作者：
Zhang B;Chan SH;Liu XQ;Shi YY;Dong ZX;Shao XR;Zheng LY;Mai ZY;Fang TL;Deng LZ;Zhou DS;Chen SN;Li M;Zhang XD
Colorectal cancer (CRC) is the third most malignant tumour worldwide, with high mortality and recurrence. Chemoresistance is one of the main factors leading to metastasis and poor prognosis in advanced CRC patients. By analysing the Gene Expression Omnibus data set, we found higher hexokinase 2 (HK2) expression levels in patients with metastatic CRC than in those with primary CRC. Moreover, we observed higher enrichment in oxaliplatin resistance‐related gene sets in metastatic CRC than in primary CRC. However, the underlying relationship has not yet been elucidated. In our study, HK2 expression was significantly elevated in CRC patients. Gene set enrichment analysis (GSEA) revealed multi‐drug resistance and epithelial‐mesenchymal transition (EMT) pathways related to high HK2 expression. Our results showed that knockdown of HK2 significantly inhibited vimentin and Twist1 expression and promoted TJP1 and E‐cadherin expression in CRC cells. Additionally, transcriptional and enzymatic inhibition of HK2 by 3‐bromopyruvate (3‐bp) impaired oxaliplatin resistance in vitro and in vivo. Mechanistically, HK2 interacts with and stabilized Twist1 by preventing its ubiquitin‐mediated degradation, which is related to oxaliplatin resistance, in CRC cells. Overexpression of Twist1 reduced the apoptosis rate by HK2 knockdown in CRC cells. Collectively, we discovered that HK2 is a crucial regulator that mediates oxaliplatin resistance through Twist1. These findings identify HK2 and Twist1 as promising drug targets for CRC chemoresistance.
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影响因子：
--
作者：
Ke TW;Hsu HL;Wu YH;Chen WT;Cheng YW;Cheng CW
通讯作者：
Cheng CW
影响因子：
3.5
作者：
Gourdier, I;Del Rio, M;Pau, B
通讯作者：
Pau, B
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
6.2
作者：
Li, Ningning;Babaei-Jadidi, Roya;Nateri, Abdolrahman S.
通讯作者：
Nateri, Abdolrahman S.
DOI：
10.3390/molecules21121730
发表时间：
2016-12-15
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lis P;Dyląg M;Niedźwiecka K;Ko YH;Pedersen PL;Goffeau A;Ułaszewski S
通讯作者：
Ułaszewski S