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Cyclin d1 depletion interferes with cancer oxidative balance and sensitizes cancer cells to senescence

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Title: Cyclin d1 depletion interferes with cancer oxidative balance and sensitizes cancer cells to senescence
Authors: Laphanuwat, P
Likasitwatanakul, P
Sittithumcharee, G
Thaphaengphan, A
Chomanee, N
Suppramote, O
Ketaroonrut, N
Charngkaew, K
Lam, EW
Okada, S
Panich, U
Sampattavanich, S
Jirawatnotai, S
Item Type: Journal Article
Abstract: 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.
Issue Date: 25-Jun-2018
Date of Acceptance: 22-May-2018
URI: http://hdl.handle.net/10044/1/60266
DOI: https://dx.doi.org/10.1242/jcs.214726
ISSN: 0021-9533
Publisher: Company of Biologists
Journal / Book Title: Journal of Cell Science
Volume: 131
Issue: 12
Copyright Statement: © 2018. Published by The Company of Biologists Ltd
Sponsor/Funder: Medical Research Council (MRC)
Worldwide Cancer Research
Cancer Research UK
Cancer Research UK
Breast Cancer Now
Breast Cancer Now
Commonwealth Scholarship Commission
Funder's Grant Number: MR/N012097/1
04-370
C9980/A9007
C37/A12011
2012NovemberPhD016
2012MayPR070
01094754
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
CDK4
Cyclin D1
FOXO3a
Retinoblastoma protein
Oxidative stress
Senescence
DNA-DAMAGE RESPONSE
TRANSCRIPTION FACTOR
TUMOR-SUPPRESSOR
IN-VIVO
MITOCHONDRIAL-FUNCTION
DEPENDENT KINASES
PHOSPHORYLATION
GENES
BIOMARKER
PROTEINS
CDK4
Cyclin D1
FOXO3a
Oxidative stress
Retinoblastoma protein
Senescence
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2018-06-07
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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