Phosphorylated P90RSK Promotes The Invasion And Metastasis In Pancreatic Cancer

Objective: Pancreatic cancer is highly malignant,prone to invasion and metastasis,and is difficult to diagnose at early stage,which is one of the reasons of bad prognosis in pancreatic cancer.It is also an urgent problem in the diagnosis and treatment of pancreatic cancer.The dissociation of cancer cells from the primary site is the most crucial step in the process of invasion and metastasis of pancreatic cancer.Therefore,trying to control the dissociation of cancer cells may control the invasion and metastasis in pancreatic cancer from the root cause.However,the molecular mechanism of invasion and metastasis of pancreatic cancer has not yet been fully elucidated.The target ribosome S6 of 4.22 of phosphorylation differential expression ratio was selected by the results of our team's phosphorylation chip.To clarify the role of this target in the process of invasion,metastasis and increment of pancreatic cancer.To explore the relationship between the target and MAPK signal pathway for the development of a more efficient and accurate new target for the treatment in pancreatic cancer.Methods: This study based on previous studies of pancreatic cancer with different proliferation and invasive ability of cells,using phosphorylation of protein microarray to detect the phosphorylated proteins blot,using Western Blot,Transwell,Wound healing,CCK-8 and other experimental methods respectively from the expression of gene and protein level verification of P90 RSK.To explore the changes of morphology,invasion and metastasis ability and proliferation and apoptosis ability of P90 RSK in pancreatic cancer,and the relationship between P90 RSK and MAPK signal transduction pathway at gene level and protein level.Results: 1.The protein expression of P90 RSK in PC-1.0 and ASPC-1 with high invasive and metastasis properties was higher then in PC-1 and CAPAN-2 with low invasive and metastasis properties;The phosphorylated protein expression of P90 RSK phosphorylated at the Thr573 site in PC-1.0 and ASPC-1 was significantly higher then in PC-1 and CAPAN-2.2.Inhibition of P90 RSK by si RNA,the total protein and phosphorylated protein expression of P90 RSK decreased significantly in PC-1.0,As PC-1,PANC-1 and PANC-1 cells.After PC-1.0,As PC-1,PANC-1 and SW1990 cells were inhibited by P90RSK,the number of cell penetrating membrane decreased significantly,invasion ability decreased significantly,cell migration rate decreased significantly,migration ability decreased significantly,and proliferation ability decreased significantly.3.There was no significant change in the expression of ERK1/2 protein in the cells after the silencing of P90 RSK with si RNA.The expression of P90 RSK protein in the cells after the silence of ERK1/2 was reduced by si RNA.Conclusion: 1.P90 RSK exists in the human source cell line and is consistent with the mouse source cell line.2.P90 RSK was similar in the expression of pancreatic cancer cells in hamsters and human pancreatic cancer cells.3.Inhibition of P90 RSK can down-regulate the proliferation,invasion and metastasis of pancreatic cancer cells.4.In pancreatic cancer,ERK1 and ERK2 regulate the proliferation,invasion and metastasis of pancreatic cancer cells by mediating P90 RSK.5.P90 RSK protein can be a new target for early diagnosis and early prevention and treatment for local invasion and distant metastasis of pancreatic cancer.