Inhibition of TRPM7 suppresses migration and invasion of prostate cancer cells via inactivation of ERK1/2, Src and Akt pathway signaling

Background: Prostate cancer is the second most common cause of cancer related death in males worldwide. Most patients show no response to androgen deprivation therapy in case of recurrence and proceed to advanced stage with metastasis. TRPM7 is reported to be upregulated in diverse types of tumors. Methods: We analyzed the expression of TRPM7 and related proteins by Western blotting analysis. We performed cell migration and invasion assay to analyze the relationship between tumor aggressiveness and TRPM7. In addition, we proceeded an animal study by using stable TRPM7 knockdown cell line in xenograft. Results: In our results, TRPM7 regulates prostate cancer cell biology including proliferation, migration and invasion through ERK1/2, PI3K/Akt and JNK signaling pathways. We produced stable TRPM7 knockdown prostate cancer cell line. To analyze the relationship between TRPM7 and tumorigenesis, we proceeded migration and invasion assay as well as xenograft model. TRPM7 down-regulated DU145 cells showed suppressed migratory and invasion ability, 0.65- and 0.05-fold, respectively. In addition, we confirmed that the anti-cancer effect of TRPM7 is mediated through inactivation of ERK1/2, Src and Akt signaling pathways by western blotting analysis. P-ERK1/2, p-Src, and p-Akt expressions were reduced to 0.66-, 0.68-, and 0.66-fold, respectively. Moreover, we treated ERK, Akt and Src inhibitors to clarify the involvement of related each protein in migration and invasion ability, and we could observe that inhibitor treated cells showed suppressed migration and invasion ability. In vivo, TRPM7 knockdown cells projected decreased cell proliferation rate. Conclusions: Taken these results together, out study suggested TRPM7 might be an essential gene for prostate cancer metastasis by regulating prostate cancer cell proliferation, migration and invasion ability.

Prostate cancer therapy; Transient receptor potential cation channel-subfamily M member 7; Migration ability; Cell proliferation; Src signaling

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