Defining the heterogeneous molecular landscape of lung cancer cell responses to epigenetic inhibition.

Autor:	Lin C; Genome Sciences, University of Washington, Seattle, WA 98105, USA., Sniezek CM; Genome Sciences, University of Washington, Seattle, WA 98105, USA., McGann CD; Genome Sciences, University of Washington, Seattle, WA 98105, USA., Karki R; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA., Giglio RM; Biomedical Engineer, Columbia University, New York, NY 10027, USA., Garcia BA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA., McFaline-Figeroa JL; Biomedical Engineer, Columbia University, New York, NY 10027, USA., Schweppe DK; Genome Sciences, University of Washington, Seattle, WA 98105, USA.; Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA.; Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 24. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1101/2024.05.23.592075
Abstrakt:	Epigenetic inhibitors exhibit powerful antiproliferative and anticancer activities. However, cellular responses to small-molecule epigenetic inhibition are heterogenous and dependent on factors such as the genetic background, metabolic state, and on-/off-target engagement of individual small-molecule compounds. The molecular study of the extent of this heterogeneity often measures changes in a single cell line or using a small number of compounds. To more comprehensively profile the effects of small-molecule perturbations and their influence on these heterogeneous cellular responses, we present a molecular resource based on the quantification of chromatin, proteome, and transcriptome remodeling due to histone deacetylase inhibitors (HDACi) in non-isogenic cell lines. Through quantitative molecular profiling of 10,621 proteins, these data reveal coordinated molecular remodeling of HDACi treated cancer cells. HDACi-regulated proteins differ greatly across cell lines with consistent (JUN, MAP2K3, CDKN1A) and divergent (CCND3, ASF1B, BRD7) cell-state effectors. Together these data provide valuable insight into cell-type driven and heterogeneous responses that must be taken into consideration when monitoring molecular perturbations in culture models. Competing Interests: Conflict of Interest: We acknowledge our ongoing collaborations and sponsored agreements with Thermo Fisher Scientific, Genentech, and AI Proteins.
Databáze:	MEDLINE
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