Expression of cyclin D1 is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in RB inactivation. Here we investigated the prosurvival 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 tested. 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 buildup of intracellular reactive oxygen species, in the cancer cells that underwent senescence upon cyclin D1 depletion, but not in CDK4 inhibition, and that ROS buildup was responsible for the senescence. Lastly, the senescence was found to be instigated by the p38/JNK-FOXO3a-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 sub-lethal level. Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway, and cancer cell succumbing to the endogenous oxidative stress.
Cyclin d1 depletion interferes with cancer oxidative balance and sensitizes cancer cells to senescence
Currently Viewing Accepted Manuscript - Newer Version Available
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 cancer oxidative balance and sensitizes cancer cells to senescence. J Cell Sci 2018; jcs.214726. doi: https://doi.org/10.1242/jcs.214726
Download citation file:
Advertisement
Introducing our new Editors
We welcome three new Editors to Journal of Cell Science - Robert Parton, Richa Rikhy and Simon Cook. You can read more about them in the Editorial from our Editor-in-Chief Michael Way.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Final registration deadline: 3 May 2024.
Workshop: Physics of the Early Embryonic Cell Divisions
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 11-14 November 2024. Application deadline: 17 May.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.
Propose a new Workshop for 2026
We are now accepting proposals for our 2026 Workshops programme. We aim to be responsive to the community and open to novel initiatives, so if you have a new idea for a biological workshop that you feel would work well, please apply. Applications deadline: 19 July 2024.