Collapsin response mediator protein 4 enhances radio-sensitivity through calcium-mediated cell signaling

Abstract Background: Radiation therapy, an effective treatment modality against various types of cancer including colorectal cancer, reduces local recurrence rate despite damaging both normal and cancer cells. However, the presence of cancer cells resistant to radiation therapy remains a major therapeutic obstacle; thus, understanding the mechanisms underlying radiation resistance is an important step toward achieving successful outcomes in cancer treatment. Hence, in the present study, radioresistant cell lines were established and the radiation-induced genetic changes associated with radiation resistance were examined.Methods: We generated radioresistant colorectal cancer cell lines and subjected them to RNA sequencing. To know the relationship between CRMP4 downregulation and radiation resistance, western blotting and flow cytometry were used.Results: CRMP4 was identified as the candidate gene associated with radiation sensitivity. The intracellular Ca2+ concentrations increased when cells were exposed to radiation, which in turn, initiated apoptosis. Decreased CRMP4 expression enhanced resistance to radiation and Ca2+ ionophore A23187. Conversely, Ca2+ deficiency by BAPTA-AM caused higher cell death in CRMP4-depleted cells than in CRMP4-expressing cells.Conclusion: Our results indicated that CRMP4 influences Ca2+ signaling pathways involved in apoptosis, and that CRMP4 is critical for radiation sensitivity in colorectal cancer as it can sensitize cancer cells to radiation therapy.