Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells

被引：102

作者：

He, Lingfeng ^{[1
]}

Zhu, Hong ^{[1
]}

Zhou, Shiying ^{[1
]}

Wu, Ting ^{[1
]}

Wu, Huan ^{[1
]}

Yang, Huan ^{[1
]}

Mao, Huiwen ^{[1
]}

SekharKathera, Chandra ^{[1
]}

Janardhan, Avilala ^{[1
]}

Edick, Ashlin M. ^{[2
]}

Zhang, Anna ^{[3
]}

Hu, Zhigang ^{[1
]}

Pan, Feiyan ^{[1
]}

Guo, Zhigang ^{[1
]}

机构：

[1] Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, 1 WenYuan Rd, Nanjing 210023, Jiangsu, Peoples R China

[2] Univ Guelph, Dept Anim Biosci, Guelph, ON, Canada

[3] Univ Guelph, Dept Psychol, Guelph, ON, Canada

来源：

EXPERIMENTAL AND MOLECULAR MEDICINE | 2018年 / 50卷

基金：

高等学校博士学科点专项科研基金;

关键词：

DNA-DAMAGE RESPONSE; HISTONE DEACETYLASES; CHECKPOINT KINASES; P53; CHK1; 5-FLUOROURACIL; CARCINOMA; APOPTOSIS; ATR; MECHANISMS;

D O I：

10.1038/s12276-018-0128-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. 5-Fluorouracil (5-FU) is widely used in the treatment of cancers, but its antineoplastic activity is limited in drug-resistant cancer cells. To investigate the detailed mechanism of 5-FU resistance, we developed a model of 5-FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell line. We found that the drug-resistant cells demonstrated high expression of TCF4 and beta-catenin, indicating an upregulated Wnt pathway. A microarray analysis revealed that the suppression of the checkpoint kinase 1 (CHK1) pathway explained the resistance to 5-FU, especially in p53 wild-type cancer cells such as HCT-8. Our data also demonstrated that the CHK1 pathway is suppressed by the Wnt pathway in 5-FU-resistant cells. In summary, we have discovered a novel mechanism for 5-FU resistance mediated by histone deacetylation, which also revealed the crosstalk between the Wnt pathway and CHK1 pathway.

引用

页码：1 / 12

页数：12

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