Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence
© 2018. Published by The Company of Biologists Ltd. Expression of cyclin D1 (CCND1) is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in inactivation of the RB tumor suppressor. Here, we investigated the pro-survival function of cyclin D1 in a nu...
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th-mahidol.451522019-08-23T17:32:43Z Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence Phatthamon Laphanuwat Pornlada Likasitwatanakul Gunya Sittithumcharee Araya Thaphaengphan Nussara Chomanee Orawan Suppramote Nuttavadee Ketaroonrut Komgrid Charngkaew Eric W.F. Lam Seiji Okada Uraiwan Panich Somponnat Sampattavanich Siwanon Jirawatnotai Kumamoto University Imperial College London Faculty of Medicine, Siriraj Hospital, Mahidol University Biochemistry, Genetics and Molecular Biology © 2018. Published by The Company of Biologists Ltd. Expression of cyclin D1 (CCND1) is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in inactivation of the RB tumor suppressor. Here, we investigated the pro-survival function of cyclin D1 in a number of cancer cell lines. We found that cyclin D1 depletion facilitated cellular senescence in several cancer cell lines. Senescence triggered by cyclin D1 depletion was more extensive than that caused by the prolonged CDK4 inhibition. Intriguingly, the senescence caused by cyclin D1 depletion was independent of RB status of the cancer cell. We identified a build-up of intracellular reactive oxygen species in the cancer cells that underwent senescence upon depletion of cyclin D1 but not in those cells where CDK4 was inhibited. The higher ROS levels were responsible for the cell senescence, which was instigated by the p38-JNKFOXO3a- p27 pathway. Therefore, expression of cyclin D1 prevents cancer cells from undergoing senescence, at least partially, by keeping the level of intracellular oxidative stress at a tolerable sublethal level. Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway and the cancer cells then succumb to the endogenous oxidative stress levels. 2019-08-23T10:32:43Z 2019-08-23T10:32:43Z 2018-06-01 Article Journal of Cell Science. Vol.131, No.12 (2018) 10.1242/jcs214726 14779137 00219533 2-s2.0-85049595436 https://repository.li.mahidol.ac.th/handle/123456789/45152 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049595436&origin=inward |
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Biochemistry, Genetics and Molecular Biology Phatthamon Laphanuwat Pornlada Likasitwatanakul Gunya Sittithumcharee Araya Thaphaengphan Nussara Chomanee Orawan Suppramote Nuttavadee Ketaroonrut Komgrid Charngkaew Eric W.F. Lam Seiji Okada Uraiwan Panich Somponnat Sampattavanich Siwanon Jirawatnotai Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
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© 2018. Published by The Company of Biologists Ltd. Expression of cyclin D1 (CCND1) is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in inactivation of the RB tumor suppressor. Here, we investigated the pro-survival function of cyclin D1 in a number of cancer cell lines. We found that cyclin D1 depletion facilitated cellular senescence in several cancer cell lines. Senescence triggered by cyclin D1 depletion was more extensive than that caused by the prolonged CDK4 inhibition. Intriguingly, the senescence caused by cyclin D1 depletion was independent of RB status of the cancer cell. We identified a build-up of intracellular reactive oxygen species in the cancer cells that underwent senescence upon depletion of cyclin D1 but not in those cells where CDK4 was inhibited. The higher ROS levels were responsible for the cell senescence, which was instigated by the p38-JNKFOXO3a- p27 pathway. Therefore, expression of cyclin D1 prevents cancer cells from undergoing senescence, at least partially, by keeping the level of intracellular oxidative stress at a tolerable sublethal level. Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway and the cancer cells then succumb to the endogenous oxidative stress levels. |
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Kumamoto University |
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Kumamoto University Phatthamon Laphanuwat Pornlada Likasitwatanakul Gunya Sittithumcharee Araya Thaphaengphan Nussara Chomanee Orawan Suppramote Nuttavadee Ketaroonrut Komgrid Charngkaew Eric W.F. Lam Seiji Okada Uraiwan Panich Somponnat Sampattavanich Siwanon Jirawatnotai |
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Phatthamon Laphanuwat Pornlada Likasitwatanakul Gunya Sittithumcharee Araya Thaphaengphan Nussara Chomanee Orawan Suppramote Nuttavadee Ketaroonrut Komgrid Charngkaew Eric W.F. Lam Seiji Okada Uraiwan Panich Somponnat Sampattavanich Siwanon Jirawatnotai |
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Phatthamon Laphanuwat |
title |
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
title_short |
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
title_full |
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
title_fullStr |
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
title_full_unstemmed |
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence |
title_sort |
cyclin d1 depletion interferes with oxidative balance and promotes cancer cell senescence |
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2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/45152 |
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1763490515291996160 |