Long-chain acyl-CoA synthetase 3 induces Akt signaling pathway that regulate the progression of prostate cancer

Abstract

Objective To investigate the molecular mechanism of ACSL3 expression in enhancing prostate cancer (PCa) cell proliferation, and to explore the potential value of ACSL3 expression in prognosis of the recurrence and metastasis of PCa. Methods Western blot was used to detect the expression of ACSL3 in different PCa cell lines. The pCDNA3.1(+)-Flag-ACSL3 plasmids were transfected into prostate cancer cells. And then, MTT assay was used to detect the alteration of cell proliferation. After over expression of ACSL3, western blot was used to detect the expression of Akt, phosphorylated Akt (p-Akt) and Matrix Metalloproteinase-9 (MMP-9) in cancer cells. Immunofluorescence staining was carried out to detect whether there was a co-localization between ACSL3 and Akt protein. Immunohistochemistry (IHC) assay was used to evaluate ACSL3 expression in tissues of PCa patients with different Gleason score. Results Western blot showed that ACSL3 protein got lower expression in localized prostate cancer cell line 22Rv1, while higher expression in hormone-independent PCa cells than in hormone-dependent PCa cells. The MTT assay demonstrated that the cell proliferation was significantly increased after ACSL3 overexpression. Moreover, overexpressing ACSL3 can also enhance p-Akt, MMP-9 expression. Immunofluorescence staining implied that there was a co-localization between ACSL3 and Akt in 22Rv1. In addition, IHC results revealed that the expression of ACSL3 protein was enhanced with the increasing of Gleason score, result in higher ACSL3 expression. Conclusion ACSL3 may induce the activation of PI3K/Akt/MMP-9 signaling pathway via the interaction between ACLS3 and Akt protein, which can enhance the proliferation of prostate cancer cells. Meanwhile, the increase expression of ACSL3 protein was correlated with higher Gleason score in patients with PCa. Key words: Prostate neoplasms; Long-chain acyl-CoA synthetase 3; Cell signaling pathway; Cell proliferation