PTPRC Targeting Inhibits Therapeutic Resistance in Colorectal Cancer

Abstract

Chemoradiotherapy (CRT) kill most of cancer cells, however small populations displaying intrinsic resistance manage to survive and propagate, raising risk of uncontrolled metastasis. To reveal a potential therapy-resistance gene responsible for such aggressiveness, we investigated the transcriptional profiling of colorectal cancer (CRC) patients. Protein tyrosine phosphatase receptor-type C (PTPRC) was found to be elevated in therapy-resistant CRC tissues as well as in metastatic tissues. PTPRC was enriched in survived CRC cells after CRT. And PTPRC expression in pre-treatment tumors was positively correlated with the poorer response to CRT, working as an independent prognostic factor for poor recurrence-free survival in these patients. Moreover, PTPRC was required for CSC properties such as self-renewing, repopulation, and metastasis. Also, PTPRC promotes survival potential and apoptosis evasion after CRT. Through screening the CSC-related signaling pathways, we discovered that PTPRC contributed to CSC-specific Wnt/β-catenin signaling by stabilizing β-catenin protein levels. Thus, our data clearly showed PTPRC as an important mediator of therapeutic resistance in CSCs.