Publication: Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence
Issued Date
2018-06-01
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ISSN
14779137
00219533
00219533
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2-s2.0-85049595436
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Cell Science. Vol.131, No.12 (2018)
Suggested Citation
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. Journal of Cell Science. Vol.131, No.12 (2018). doi:10.1242/jcs214726 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45152
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Title
Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence
Abstract
© 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.