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

Abstract

Abstract Metastasis remains the leading 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 shown in the development of tumors, and GLDC is up-regulated in cancers such as lung cancer, prostate cancer, bladder cancer, and cervical cancer. However, the exact role of GLDC in colorectal cancer (CRC) progression remains to be elucidated. The aim of our study was to explore the action of GLDC in CRC metastasis. The GSE75117 database was used to investigate GLDC expression in tumor center and invasive front tissues and found that GLDC expression level was higher in invasive front tissue. GLDC expression level was negatively correlated with CRC patient prognosis. In vitro studies showed that GLDC could promote invasion and migration of CRC cells by inhibiting the Hippo signaling pathway and modulating the EMT process. Blocking the Hippo signaling pathway with Verteporfin reduced the effect of GLDC on CRC metastasis. In vivo metastasis experiments further confirmed that tail vein injection of GLDC+/+ cells promoted lung metastasis, compared with normal CRC cells. The results of this study suggested that GLDC promotes EMT through Hippo signaling pathway in CRC metastasis, providing a new therapeutic target for CRC metastasis.