1. MACC1 facilitates chemoresistance and cancer stem cell-like properties of colon cancer cells through the PI3K/AKT signaling pathway
- Author
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Jian-Kai Wang, Hongyi Cai, Yongguo Hu, Wen Ma, Wen-Juan Wang, Shi-Fang Feng, Guo-Ying Miao, Bin-Bin Du, and Lijuan Zhang
- Subjects
cancer stem cells ,0301 basic medicine ,Homeobox protein NANOG ,Cancer Research ,Colorectal cancer ,Gene Expression ,Biology ,medicine.disease_cause ,Biochemistry ,metastasis-associated colon cancer 1 ,Metastasis ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Cancer stem cell ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,5-fluorouracil ,Molecular Biology ,Oncogene ,chemoresistance ,Cancer ,Articles ,medicine.disease ,Cell biology ,030104 developmental biology ,colon cancer ,Oncology ,Drug Resistance, Neoplasm ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Protein kinase B signaling ,Colonic Neoplasms ,Neoplastic Stem Cells ,protein kinase B ,Molecular Medicine ,Fluorouracil ,Carcinogenesis ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
With regards to colon cancer, resistance to 5-fluorouracil (5-FU)-based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis-associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC-like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5-FU; subsequently, CSC-like properties and 5-FU sensitivity were investigated. Within 5-FU-resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3-kinase/protein kinase B signaling pathway may be associated with 5-FU resistance and CSC-like properties via MACC1.
- Published
- 2017