High PTPRC expression in Colorectal Cancer Cells Enhances Stemness and Radioresistance

Abstract

Radiotherapy is an essential module of primary, adjuvant, and palliative treatment for most types of solid cancer. However, small subpopulations survive radiotherapy and succeed at colonizing distant organs, preventing a permanent cure. Here we firstly report that protein phosphatase receptor C (PTPRC), a metastatic gene whose expression increases in response to radiation, drives therapeutic resistance phenotypes, such as increased clonogenic survival and reduced apoptosis in colorectal cancer cells. Interestingly, PTPRC is preferentially expressed in cancer stem-like cells (CSCs) than bulk tumor cells and promotes certain CSC properties, including tumor initiation, repopulation, metastatic growth, and therapeutic resistance. Mechanistically, PTPRC promotes β-catenin dephosphorylation, thereby preventing its degradation and enhancing the transcriptional activity of Wnt/β-catenin signaling. Correspondingly, PTPRC deletion combined with radiotherapy synergistically reduces metastasis and primary tumor burden than radiation alone, revealing PTPRC as an important mediator of therapeutic resistance in CSCs.