Defining the Heterogeneous Molecular Landscape of Lung Cancer Cell Responses to Epigenetic Inhibition

Overview

Journal bioRxiv

Date 2024 Jun 10

PMID 38853901

Authors

Chuwei Lin

Catherine M Sniezek

Christopher D McGann

Rashmi Karki

Ross M Giglio

Benjamin A Garcia

Jose L McFaline-Figeroa

Devin K Schweppe

Affiliations

Soon will be listed here.

Abstract

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.

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