The Biological Function And Molecular Mechanism Of REGγ In Colon Cancer Development

Cancer is always the killer of our human. Among those deadly disease, the colon cancer ranks the third one, owning to its high lethality rate. Although a number of cancer-related genes and pathways have been demonstrated, there still remains largely unknown about more detailed molecular mechanism in carcinogenesis. As an important proteasome coactivator, REGy is actively involved in many regulative pathways. It has been showed that REGy is closely related to various kinds of cancers, including colon cancer. Based on this, we want to explore the biological functions of REGy in colon cancer development.To obtain satisfying answer in physiological condition, we established colon cancer model based on wild-type and REGy-knockout mice and found there is an obvious difference in tumorigenesis between those two types of mice. Moreover, the subsequent study proved that REGy can show its cancer-promoting ability by increase the cell proliferation rate. Next, we found the Hippo pathway plays an important role in REGy-dependent colon cancer in both tissue level and cellular level. In detail, we discovered that REGy can lead to the degradation of Mstl and result in the decline of phosphorylated YAP. When all of those happens, YAP can translocate into the nucleus and perform the function of transcription coactivator. In the end, numerous YAP downstream target genes, which mainly promote the proliferation of the cell, will have a high expression in wild-type rather than the REGy-knockout mice and finally contribute to the phenotype described in the beginning. At last, we also detect the influence of REGy on colon stem cell and found that REGy can promote the expression of marker genes of colon stem cell.In conclusion, REGy can participate in the development of colon cancer through its regulation on Hippo pathway and thus could be a new target gene for colon cancer therapy.