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The histone chaperone complex FACT promotes proliferative switch of G 0 cancer cells
Author(s) -
Bi Ling,
Xie Chanlu,
Yao Mu,
Thae Hnit Su Su,
Vignarajan Soma,
Wang Yilun,
Wang Qian,
Xi Zhichao,
Xu Hongxi,
Li Zhong,
Souza Paul,
Tee Andrew,
Wong Matthew,
Liu Tao,
Zhao Xiaodong,
Zhou Jia,
Xu Ling,
Dong Qihan
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32065
Subject(s) - cell cycle , chromatin , cancer research , biology , cancer cell , ectopic expression , microbiology and biotechnology , dna repair , cell cycle checkpoint , cell growth , cell , dna damage , histone , cancer , gene silencing , cell culture , dna , genetics , gene
Cancer cell repopulation through cell cycle re‐entry by quiescent (G 0 ) cell is thought to be an important mechanism behind treatment failure and cancer recurrence. Fa cilitates C hromatin T ranscription (FACT) is involved in DNA repair, replication and transcription by eviction of histones or loosening their contact with DNA. While FACT expression is known to be high in a range of cancers, the biological significance of the aberrant increase is not clear. We found that in prostate and lung cancer cells FACT mRNA and protein levels were low at G 0 compared to the proliferating state but replenished upon cell cycle re‐entry. Silencing of FACT with Dox‐inducible shRNA hindered cell cycle re‐entry by G 0 cancer cells, which could be rescued by ectopic expression of FACT. An increase in SKP2, c‐MYC and PIRH2 and a decrease in p27 protein levels seen upon cell cycle re‐entry were prevented or diminished when FACT was silenced. Further, using mVenus‐p27K − infected cancer cells to measure p27 degradation capacity, we confirm that inhibition of FACT at release from quiescence suppressed the p27 degradation capacity resulting in an increased mVenus‐p27K − signal. In conclusion, FACT plays an important role in promoting the transition from G 0 to the proliferative state and can be a potential therapeutic target to prevent prostate and lung cancer from progression and recurrence.