Dysregulated expression of microtubule-associated protein tau (MAPT) has been reported in a variety of human cancers. However, whether and how Tau influences hepatocellular carcinogenesis remains elusive. This study was aimed to investigate the role and the underlying mechanism of Tau in the proliferation, invasion, migration and sorafenib sensitivity of hepatocellular carcinoma (HCC) cells. An increased level of Tau was found in the primary tumor samples of HCC compared with the adjacent normal liver tissues, and the increase of Tau was positively correlated with p62 evidenced by the data obtained from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and human samples from HCC patients. The high Tau expression was also correlated with a poorer survival in HCC patients demonstrated by using the GEPIA survival analysis and OncoLnc database. Further studies showed that Tau overexpression promoted the growth, invasion and migration and decreased sorafenib sensitivity in HepG2 and Huh7 cells; Tau also accelerated growth of xenograft tumors with blockage of autophagosome-lysosome fusion. Finally, overexpressing Tau inhibited AMPK, which contributed to Tau-induced promotion of hepatocellular carcinogenesis. In conclusion, our study provides the proof-of-concept evidence validating Tau as an attractive HCC target.
Keywords: Autophagy; Hepatocellular carcinoma; Microtubule-associated protein tau; p62.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.