Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium‑mediated cell signaling
| Autor: | Sang Yoon Park, Jong-Tae Kim, Suk Ran Yoon, Eun Sun Park, Kyoung Eun Baek, Yo Sep Hwang, Bo Yeon Kim, Haiyoung Jung, Hee Jun Cho, Hyang Ran Yoon, Hee Gu Lee |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Muscle Proteins Radiation Tolerance 03 medical and health sciences mitochondrial membrane potential 0302 clinical medicine Radiation sensitivity Cell Line Tumor Radioresistance medicine Humans Radiosensitivity Cell Death Sequence Analysis RNA Chemistry Cancer Articles General Medicine Cell cycle medicine.disease radioresistance 030104 developmental biology colon cancer Oncology Apoptosis 030220 oncology & carcinogenesis Colonic Neoplasms Cancer cell Cancer research Calcium calcium influx CRMP4 Signal Transduction |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2021.7957 |
| Popis: | 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 (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. |
| Databáze: | OpenAIRE |
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