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

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.

Intra-tumoral YAP and TAZ heterogeneity drives collective NSCLC invasion that is targeted by SUMOylation inhibitor TAK-981.

Non-small cell lung cancer (NSCLC) collective invasion is supported by cooperativity of proliferative (follower) and invasive (leader) cells. H1299-isolated follower cells exhibit higher Yes-associated protein (YAP) expression, while leader cells were found to express elevated transcriptional coactivator with PDZ-binding motif (TAZ/WWTR1) expression. Suppressing TAZ (not YAP) in leader cells reduced invasion.