Open AccessWnt pathway is involved in 5-FU drug resistance of colorectal cancer cells
Author(s) -
Lingfeng He,
Hong Zhu,
Shiying Zhou,
Ting Wu,
Huan Wu,
Huan Yang,
Huiwen Mao,
Chandra SekharKathera,
Avilala Janardhan,
Ashlin M. Edick,
Anna Zhang,
Zhigang Hu,
Feiyan Pan,
Zhigang Guo
Publication year - 2018
Publication title -
experimental and molecular medicine/experimental and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.703
H-Index - 82
eISSN - 2092-6413
pISSN - 1226-3613
DOI - 10.1038/s12276-018-0128-8
Subject(s) - wnt signaling pathway , colorectal cancer , cancer research , drug resistance , cancer cell , cancer , mouse model of colorectal and intestinal cancer , catenin , biology , medicine , signal transduction , microbiology and biotechnology , genetics
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 β-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.