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

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 c...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877015/
https://www.ncbi.nlm.nih.gov/pubmed/33655336
http://dx.doi.org/10.3892/or.2021.7957
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author 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
author_facet 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
author_sort Park, Sang Yoon
collection PubMed
description 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 Ca(2+) influx, collapse of mitochondrial membrane potential, and cytochrome c release into the cytosol were increased, followed by apoptosis induction. Radiation treatment- or Ca(2+) 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 Ca(2+) chelator, resulted in radiation resistance. Conversely, Ca(2+) 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 Ca(2+)-mediated cell death pathways under radiation exposure and that CRMP4 may be a therapeutical target for colon cancer treatment.
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spelling pubmed-78770152021-02-24 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 Oncol Rep Articles 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 Ca(2+) influx, collapse of mitochondrial membrane potential, and cytochrome c release into the cytosol were increased, followed by apoptosis induction. Radiation treatment- or Ca(2+) 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 Ca(2+) chelator, resulted in radiation resistance. Conversely, Ca(2+) 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 Ca(2+)-mediated cell death pathways under radiation exposure and that CRMP4 may be a therapeutical target for colon cancer treatment. D.A. Spandidos 2021-04 2021-01-29 /pmc/articles/PMC7877015/ /pubmed/33655336 http://dx.doi.org/10.3892/or.2021.7957 Text en Copyright: © Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
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
Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title_full Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title_fullStr Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title_full_unstemmed Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title_short Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
title_sort collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium-mediated cell signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877015/
https://www.ncbi.nlm.nih.gov/pubmed/33655336
http://dx.doi.org/10.3892/or.2021.7957
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