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

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Title
Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
Author(s)
Sang Yoon Park; Jong-Tae Kim; Eun Sun Park; Yo Sep Hwang; Hyang Ran Yoon; Kyung Eun Baek; Haiyoung JungSuk Ran YoonBo Yeon KimHee Jun ChoHee Gu Lee
Bibliographic Citation
Oncology Reports, vol. 45, no. 4, pp. 6-6
Publication Year
2021
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.
Keyword
CRMP4RadioresistanceColon cancerCalcium influxMitochondrial membrane potential
ISSN
1021-335X
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/or.2021.7957
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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