HIF-1α affects invasion and metastasis of prostate cancer by regulating invadopodia formation

Abstract

Background Prostate cancer is an important disease that threatens the health of middle-aged and older men. In tumor diseases, HIF-1α can affect tumor proliferation, invasion, and metastasis by regulating the expression of various types of molecules and thus activating related signaling pathways. In this study, we explored the mechanisms by which HIF-1α affects prostate cancer invasion and metastasis. Method Exploration of the mechanisms by which HIF-1α affects prostate cancer invasion and metastasis using transcriptome sequencing. Detection of invadopodia-related molecules using Western blot. The formation of invadopodia in prostate cancer cells and the localization of HIF-1α and TKS5 were detected using immunofluorescence. Detection of extracellular matrix degradation by invadopodia in prostate cancer using gelatin degradation assays. Validation of the interaction of HIF-1α with TKS5 using Co-IP. Results HIF-1α is highly expressed in prostate cancer. HIF-1α can affect the proliferation, invasion, and metastasis of prostate cancer. We found that HIF-1α was associated with cell motility as well as extracellular matrix degradation in prostate cancer, suggesting that HIF-1α may promote prostate cancer invasion and metastasis by affecting the formation of invadopodia. Degradation of extracellular matrix by prostate cancer cells was reduced after knockdown of HIF-1α, as was the formation of invadopodia. The results of Western blot showed that the expression of TKS5 and MMP9 was decreased after knockdown of HIF-1α. The results of Co-IP and immunofluorescence suggested that HIF-1α could interact with TKS5 near the nuclear membrane. Conclusion In the present study, we demonstrated that HIF-1α was able to influence the invasive and metastatic ability of prostate cells by affecting the expression of TKS5 and thus the formation of invadopodia. We also found that HIF-1α was able to interact with TKS5 near the nuclear membrane. These results provide a new direction for the exploration of invadopodia in the prostate cancer.