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

Fengqiang Zhou; Yanmei Qi; Zhen Geng; Baozhong Ding; Lei Liu

doi:10.2174/1386207326666230209093639

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

Comb Chem High Throughput Screen. 2023 Feb 9. doi: 10.2174/1386207326666230209093639. Online ahead of print.

Authors

Fengqiang Zhou¹, Yanmei Qi², Zhen Geng¹, Baozhong Ding¹, Lei Liu¹

Affiliations

¹ Department of Gastrointestinal Surgery, Binzhou People's Hospital, Binzhou City, Shandong, 256600, China.
² Department of Gastroenterology, Binzhou People's Hospital, Binzhou City, Shandong, 256600, China.

PMID: 36757043
DOI: 10.2174/1386207326666230209093639

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.

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.

Keywords: CD44; Colorectal cancer; EpCAM; Oxaliplatin chemoresistance; Tumor proliferation; Wnt/β-Catenin signaling.