TGF-β1-mediated intercellular signaling fuels cooperative cellular invasion.

ABSTRACT: Intratumoral heterogeneity drives cancer progression and influences treatment outcomes. The mechanisms underlying how cellular subpopulations communicate and cooperate to impact progression remain largely unknown. Here, we use collective invasion as a model to deconstruct processes underlying non-small cell lung cancer subpopulation cooperation. We reveal that collectively invading packs consist of heterogeneously cycling and non-cycling subpopulations using distinct pathways. We demonstrate that the follower subpopulation secretes transforming growth factor beta one (TGF-β1) to stimulate divergent subpopulation responses-including proliferation, pack cohesion, and JAG1-dependent invasion-depending on cellular context. While isolated followers maintain proliferation in response to TGF-β1,

SUBMITTER: Khatib TO 

PROVIDER: S-EPMC11951108 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature