Hepatic stellate cells induce hepatocellular carcinoma cell resistance to sorafenib through the laminin‐332/α3 integrin axis recovery of focal adhesion kinase ubiquitination
Amalia Azzariti, Serena Mancarella, Letizia Porcelli, Anna Elisa Quatrale, Alessandra Caligiuri, Luigi Lupo, Francesco Dituri, Gianluigi Giannelli – 17 September 2016 – In patients with hepatocellular carcinoma (HCC) receiving sorafenib, drug resistance is common. HCC develops in a microenvironment enriched with extracellular matrix proteins including laminin (Ln)‐332, produced by hepatic stellate cells (HSCs). Ln‐332 is the ligand of α3β1 and α6β4 integrins, differently expressed on the HCC cell surface, that deliver intracellular pathways.