Melanoma is a malignant tumor of cutaneous melanocytes that is characterized by high grade malignancy, rapid progression and high mortality. Thus far, its specific etiological mechanism has been unclear. In this study, we discovered that Lyn kinase expression was up-regulated in melanoma tissues and cells. The function of Lyn was determined by knocking down its expression with a lentivirus containing Lyn shRNA and upregulating its expression with pcDNA3.1-Lyn in the melanoma cell lines M14 and A375. The results showed that Lyn knockdown could significantly inhibit the proliferation, migration and invasiveness through its inhibition of apoptosis and autophagy via the PI3K/Akt pathway in melanoma cell lines. This was further confirmed by treatment with PI3K inhibitor BEZ235. Up-regulation of Lyn promoted the expression of p-Akt and Cyclin D1. Additionally, we investigated the effects of Lyn inhibitor Bafetinib on melanoma cells and the results were consistent with Lyn knockdown. Collectively, our results indicated that Lyn plays a carcinogenic role in multiple cellular functions during melanoma development through regulating apoptosis and autophagy via the PI3K/Akt pathway and may be a valuable potential target for the clinical treatment of melanoma.
Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.