In vitro results showed that (1) HCC cells recruit PTFs and promote their differentiation to a CAF-like αSMA+ myofibroblastic phenotype; (2) silencing ATX in HCC cells or inhibiting LPA using a pan-LPA inhibitor prevented PTF transdifferentiation; and (3) transdifferentiated PTFs enhanced the proliferation, migration and invasion of HCC cells. The gene discussed is ENPP2; the disease is hepatocellular carcinoma.