Role Of Sin1 In Prostate Cancer

Prostate cancer is one of the most common malignant tumor diseases in men,and its malignancy and mortality are only lower than skin cancer in the Western male population.Although the incidence rate of Prostate cancer in China is relatively low,the prevalence of prostate cancer in China has increased due to the effects of high-fat diet,smoking,and aging.The PI3K-AKT-mTORC signaling pathway is the most important signaling pathway in tumorigenesis and cancer development.Activation of this signaling pathway is related to the proliferation and differentiation of cancer cells.Sin1 is an important component of the mTORC2 complex,which is upstream of the AKT signal pathway.Previous studies have illuminated the effects of mTOR and AKT signaling on cancer,but less on the function of Sin1 itself and its role in related signaling pathways.This study focused on the activation of the AKT signaling pathway by Sin1 and then explored the relationship between Sin1 and prostate tumorigenesis and cancer development.In this study,the expression of Sin1 in human prostate cancer tissues is first examined by tissue microarray,which had a significant overexpression of Sin1 in prostate tumor tissues.Secondly,the expression of Sin1 and PI3K-AKT signaling pathways is investigated using specific signaling pathway inhibitors,and it is confirmed that phosphorylation of Sin1 is the key to the activation of AKT signaling.Changes in the PI3K-AKT-mTORC signaling pathway can also be observed by using of commercialized siRNA and overexpression vectors to alter the background levels of Sin1.In addition,the researchers use MTT assay and invasion assay to confirm that Sin1 can promote the cell viability and invasion ability of prostate cancer cells,which confirmes that Sin1 plays a positive role in promoting prostate cancer.Finally,this study briefly examines the relationship between Sin1 and sex hormones.It is initially confirmed that estrogen can stimulate expression and phosphorylation of Sin1 in PC 3 prostate cancer cell lines.And androgen can stimulate protein expression and phosphorylation of Sin1 in LNCaP prostate cancer cell lines,but the similar situation does not occur in the C4-2 prostate cancer cell line,which is a type of hormone-independent cells.This suggests that Sin1 expression and activation may be dependent on hormones.Therefore,we propose the biological model of this study,that is,under the stimulation of hormones,the relevant receptors on the membrane of prostate cancer cells received signals.The second messenger stimulates the activation of the PI3 K signal.During the activation process,the background level and phosphorylation level of Sin1 are increased and then participate in the reconstruction of mTORC2 complex,which stimulates downstream AKT signal,enhances the viability and invasion ability of tumor cells and ultimately leads to tumor development.