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

Park,Sang Yoon; Kim,Jong-Tae; Park,Eun Sun; Hwang,Yo Sep; Yoon,Hyang Ran; Baek,Kyoung Eun; Jung,Haiyoung; Yoon,Suk Ran; Kim,Bo Yeon; Cho,Hee Jun; Lee,Hee Gu

doi:10.3892/or.2021.7957

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

Authors:
- Sang Yoon Park
- Jong-Tae Kim
- Eun Sun Park
- Yo Sep Hwang
- Hyang Ran Yoon
- Kyoung Eun Baek
- Haiyoung Jung
- Suk Ran Yoon
- Bo Yeon Kim
- Hee Jun Cho
- Hee Gu Lee
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Affiliations: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea, Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
Published online on: January 29, 2021 https://doi.org/10.3892/or.2021.7957
Article Number: 6
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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