A metabolite-centered view of hepatic stellate cells in MASLD-related liver cancer
The study by Labrecque and colleagues places hepatic stellate cells at the center of metabolic dysfunction-associated steatotic liver disease (MASLD)–related hepatocellular carcinoma (HCC) by linking spatially defined stellate-cell subpopulations to geranylgeranyl pyrophosphate (GGPP)–dependent YES-associated protein (YAP) activation. Its most important contribution is not merely the identification of a statin-sensitive GGPP–Rho–YAP axis, but also the suggestion that tumor–stroma crosstalk in MASLD-HCC is organized spatially within the peritumoral pseudocapsule. This Perspective article discusses how these findings reshape our understanding of hepatic stellate cell (HSC) heterogeneity, statin chemoprevention, metabolic signaling, and future therapeutic strategies in cirrhotic and non-cirrhotic MASLD-HCC.
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