Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium?mediated cell signaling.

ABSTRACT: Radiation therapy is an effective treatment against various types of cancer, but some radiation?resistant cancer cells remain a major therapeutic obstacle; thus, understanding radiation resistance mechanisms is essential for cancer treatment. In this study, we established radiation?resistant colon cancer cell lines and examined the radiation?induced genetic changes associated with radiation resistance. Using RNA?sequencing analysis, collapsin response mediator protein 4 (CRMP4) was identified as the candidate gene associated with radiation sensitivity. When cells were exposed to radiation, intracellular Ca²⁺ influx, collapse of mitochondrial membrane potential, and cytochrome c release into the cytosol were increased, followed by apoptosis induction. Radiation treatment? or Ca²⁺ ionophore A23187?induced apoptosis was significantly inhibited in CRMP4?deficient cells, including radiation?resistant or CRMP4?shRNA cell lines. Furthermore, treatment of CRMP4?deficient cells with low levels (<5 µM) of BAPTA?AM, a Ca²⁺ chelator, resulted in radiation resistance. Conversely, Ca²⁺ deficiency induced by a high BAPTA?AM concentration (>10 µM) resulted in higher cell death in the CRMP4?depleted cells compared to CRMP4?expressing control cells. Our results suggest that CRMP4 plays an important role in Ca²⁺?mediated cell death pathways under radiation exposure and that CRMP4 may be a therapeutical target for colon cancer treatment.

SUBMITTER: Park SY 

PROVIDER: S-EPMC7877015 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature