APPL1 could directly bind to both STAT3 and leptin receptor to elevate leptin-induced phosphorylation of Akt, ERK1/2 and STAT3 in breast cancer MCF-7 and human hepatocellular carcinoma HepG2 [27], while a reverse function in rat hepatocellular carcinoma proliferation was also reported, this is, via a p38-MAPK-dependent signalling pathway in vitro to reduce serum-stimulated H4IIE HCC cell proliferation [28]. The gene discussed is LEPR; the disease is breast cancer.