Abstract: ［Abstract］ Objective〖HTSS〗To investigate the molecular mechanism of Hippo pathway regulating colorectal tumor metastasis.
〖HTH〗〖WTHZ〗Methods〖HTSS〗Download the clinical data and the expression values of YAP1, TAZ and Ascl2 of 276 colorectal cancer patients in the TCGA database, the expression patterns in colorectal cancer tissues, corresponding adjacent tissues, different M and T stages of colorectal cancer tissues, overall survival(OS) and disease-free survival(disease-free survival, DFS) were analyzed. The overexpression vector of Hippo pathway activating factor MST1 and MST2 was constructed and transfected into SW480 cells. The target genes YAP1 and TAZ of the Hippo pathway and the epithelial-mesenchymal transition(EMT) related factors Ascl2 were detected by Western blot and quantitative real-time polymerase chain reaction(qPCR).
〖HTH〗〖WTHZ〗Results〖HTSS〗The expression of YAP1, TAZ and Ascl2 in colorectal cancer was significantly higher than that in paracancerous tissues, and the expression level of YAP1, TAZ and Ascl2 was increased with the distant metastasis and infiltration of tumor. The 5-year OS and DFS of patients with high expression of YAP1, TAZ and Ascl2 were significantly lower than those of patients with low expression. Overexpression of Hippo pathway kinase MST1 and MST2 resulted in increased phosphorylation of YAP1/TAZ, decreased expression of non-phosphorylated YAP1/TAZ, inhibition of EMT-related factors Ascl2 and N-cadherin, and increased E-cadherin expression. Transwell experiments confirmed that MST1/2 overexpression inhibited colon cancer cell migration and invasion. Luciferase reporter system showed that overexpression of MST1/2 inhibited the transcriptional activity of Ascl2 promoter, indicating that transcriptional regulation of Ascl2 is inhibited by Hippo pathway.
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗Ascl2 is a downstream target of Hippo pathway, Activation of Hippo pathway can inhibit the EMT of colorectal cancer and further hinder the occurrence of tumor metastasis, and the study provided a new basis for the mechanism of colorectal cancer metastasis.

Key words: colorectal neoplasms, neoplasm metastasis;Hippo pathway, Ascl2