AHSA1 promotes proliferation and EMT by regulating ERK/CALD1 axis in hepatocellular carcinoma

This is the authors' abstract. We don't add key points for this paper.

Background Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely unknown. The purpose of this study is to elaborate the role of AHSA1 in HCC development. Methods Real-Time PCR, Western blotting, and Immunohistochemistry were used to determine the mRNA and protein expression of AHSA1 in liver epithelial cells, HCC cells, and tissues. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated the role of AHSA1 in the proliferation, invasion, metastasis, and epithelial-mesenchymal transition of HCC. To explore the molecular mechanism of AHSA1 in HCC, Western blotting, coimmunoprecipitation assay, and mass spectrometer assay were performed. Results Actually, we found AHSA1 was significantly upregulated in HCC tissues and cell lines, and was correlated with the poor prognosis of HCC patients. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated AHSA1 promoted the proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) of HCC. Moreover, the mechanistic study indicated that AHSA1 recruited ERK1/2 and promoted the phosphorylation and inactivation of CALD1, while ERK1/2 phosphorylation inhibitor, SCH772984, reversed the role of AHSA1 in the proliferation and EMT of HCC. Furthermore, we demonstrated the knockdown of CALD1 reversed the inhibition of proliferation and EMT by knocking AHSA1 in HCC. We also illustrated a new molecular mechanism associated with AHSA1 in HCC that was independent of HSP90 and MEK1/2. Conclusions In summary, AHSA1 may play an oncogenic role in HCC by regulating ERK/CALD1 axis and serve as a novel therapeutic target for HCC.