title: Facilitates chromatin transcription complex is an "accelerator" of tumor transformation and potential marker and target of aggressive cancers.
abstract: The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACT's role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Garcia
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Miecznikowski
authors.forename: Alfiya
authors.initials: A
authors.lastname: Safina
authors.forename: Mairead
authors.initials: M
authors.lastname: Commane
authors.forename: Anja
authors.initials: A
authors.lastname: Ruusulehto
authors.forename: Sami
authors.initials: S
authors.lastname: Kilpinen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Leach
authors.forename: Kristopher
authors.initials: K
authors.lastname: Attwood
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Seamus
authors.initials: S
authors.lastname: Degan
authors.forename: Angela R
authors.initials: AR
authors.lastname: Omilian
authors.forename: Olga
authors.initials: O
authors.lastname: Guryanova
authors.forename: Olympia
authors.initials: O
authors.lastname: Papantonopoulou
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Buck
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Katerina V
authors.initials: KV
authors.lastname: Gurova
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C073537:SSRP1 protein, human; C489489:SUPT16H protein, human; C465039:Supt16 protein, mouse; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C070454:Ssrp1 protein, mouse