REGγ Promotes Colon Cancer Tumorigenesis By Regulating Hippo Pathway

Cancer is one of the most difficult disease to cure in the world in the past few years.Especially,colon cancer has the highest rate of morality.People have done a lot of research on colon cancer for several years,and they found some signaling pathways about this cancer,such as Hippo signaling pathway,Wnt signaling pathway and cell cycle signaling pathway.In recent years,REGy have been known as 20S proteasome activating factor,and some papers have shown that REGy is involved in some signaling pathway which is related with cancers.Therefore,in order to study the molecular mechanism,the ways of REGy affects the development of colon cancer,we started this subject which is based on the biological function of REGy and the signaling pathway related with colon cancer.First,we established the chemical-induced AOM-DSS colon cancer model on REGγ－WT mouse and REGy-KO mouse.We discovered that REGy plays an important role in the development of colon cancer.Then we did experiments to confirm that REGy promote cell proliferation both on tissue level and cell level.Continuously,we explored that REGy have some relationship with Hippo signaling pathway.When REGy has high expression,YAP will also has high expression.Lots of papers shows that YAP is a transcription factor coactivator in nuclear.If YAP is transported into nuclear,the downstream target genes will be activated to express,which lead to the abnormal cell proliferation,and finaly cancers will occur.We concentrated on the key kinase LATS1 in Hippo pathway.Then we found that REGy is involved in the degradation of LATS1.At last,we did the xenograft experiment on nude mouse,then we confirmed that REGy regulate the transport of YAP into the nuclear by involving the degradation of LATS1,to influent the expression of downstream target genes,finaly affects the development of colon cancer.