GLDC promotes colorectal cancer metastasis through epithelial-mesenchymal transition mediated by Hippo signaling pathway.

Abstract

Cancer metastasis remains a major cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) plays a decisive role in cancer metastasis. Recently, abnormal expression of Glycine Decarboxylase (GLDC) has been demonstrated in tumor progression, and GLDC is up-regulated in cancers, such as lung, prostate, bladder, and cervical cancers. However, the exact role of GLDC in colorectal cancer (CRC) progression remains to be elucidated. The aim of our study was to explore the role of GLDC in CRC metastasis. The GSE75117 database was used to investigate GLDC expression in tumor center and invasive front tissues and we found that GLDC expression levels were higher in theinvasive front tissue. GLDC expression levels were negatively correlated with the prognosis of CRC patients. In vitro studies have showed that GLDC can promote invasion and migration of CRC cells by inhibiting the Hippo signaling pathway and regulating the EMT process. Blocking the Hippo signaling pathway with Verteporfin reduced the effect of GLDC on CRC metastasis. In vivo metastasis assays further confirmed that tail vein injection of GLDC+/+ cells induced morelung metastasis, compared to normal CRC cells. The results of this study suggest that GLDC promotes EMT through the Hippo signaling pathway, providing a new therapeutic target for CRC metastasis.