The histone chaperone complex FACT promotes proliferative switch of G₀ cancer cells

Abstract

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.