Activation of Wnt/β-Catenin signaling in EpCAMhigh/CD44+ cells endow colorectal cancer with tumor proliferation and oxaliplatin chemoresistance

Abstract

Aims: The present study investigated the exact proportion, the extent of in vitro proliferation potential, and oxaliplatin chemoresistance of EpCAMhigh/CD44+ cancer stem cells in colorectal cancer. Its underlying mechanism was also explored. Background: Colorectal cancer stem cells (CSC) play crucial roles in tumorigenicity and chemoresistance. Multiple studies have shown that JAK/STAT, NOTCH, and Wnt/-catenin pathways, associated with tumour recurrence and metastasis, contribute to the proliferation and maintenance of CSCs. CSCs become resistant to chemo-radiotherapies by improving DNA damage repair, changing cell cycle checkpoints, and scavenging reactive oxygen species, resulting in a bad patient prognosis. Objective: This work was carried out to determine the precise fraction, the degree of in vitro proliferation capability, and the level of oxaliplatin chemoresistance exhibited by EpCAMhigh/CD44+ cancer stem cells in colorectal cancer. The research was also done to investigate its underlying process. Methods: Fluorescence-activated cell sorting (FACS) was applied to isolate the EpCAMhigh/CD44+ populations from three human colorectal cancer cell lines (HCT116, HT29, and LoVo), and we quantified the average proportion of the EpCAMhigh/CD44+ cells in every cell lines. The comparison of their proliferation ability and the chemoresistance to oxaliplatin with the parental cells was estimated by CCK8 assay. The activated signaling pathway was tested by Western Blotting. result: EpCAMhigh/CD44+ subpopulation comprise about 4.98±1.24% of the total human colorectal cancer cell lines, and the EpCAMhigh/CD44+ cells exhibited a highly better proliferation ability and stronger oxaliplatin chemoresistance than the parental cells. Wnt/β-catenin signaling pathway is activated in EpCAMhigh/CD44+ HCT116 cells. Results: EpCAMhigh/CD44+ subpopulation comprises about 4.98±1.24% of the total human colorectal cancer cell lines, and the EpCAMhigh/CD44+ cells exhibited a highly better proliferation ability and stronger oxaliplatin chemoresistance than the parental cells. The wnt/β-catenin signaling pathway is activated in EpCAMhigh/CD44+ HCT116 cells conclusion: Activation of Wnt/β-Catenin signaling in EpCAMhigh/CD44+ cells endow colorectal cancer with tumor proliferation and oxaliplatin chemoresistance. Conclusion: Activation of Wnt/β-Catenin signaling in EpCAMhigh/CD44+ cells endow colorectal cancer with tumor proliferation and oxaliplatin chemoresistance.