| 摘要: | Colorectal cancer (CRC) is one of the major causes of mortality associated with cancer. Glucose-regulated protein 94 (GRP94) is the essential endoplasmic reticulum-stress response protein related to development of several cancers. The GRP94’s role in progression of CRC has not been fully elucidated, yet. We found that knockdown of GRP94 decreased cell growth, migration and invasion of CRC cells and tumor growth in the xenograft mouse model. Overexpression ETV1 in GRP94-KD cells induced cell growth and migratory ability. Protein level of cyclooxygenase-2, vimentin, β-catenin and N-cadherin were reduced in GRP94-KD cells while level of E-cadherin was increased. To dissect the mechanism, nanostring gene expression analysis was used and ETV1 was found to be a downstream target of GRP94. Protein levels of MAPK pathway were checked and levels of JNK/p-JNK, ERK/p-ERK, and P38/p-P38 were attenuated in GRP94-KD cells. Transcriptional and translational expressions of ETV1 were reduced after treatment of inhibitors for ERK and P38 while expression of ETV1 was not changed at transcriptional level in cells treated with JNK inhibitor. The results indicate that knockdown of GRP94 repressed growth, migration, and CRC tumorigenesis by regulating ETV1 and MAPK pathway. In conclusion, GRP94 may play a vital role in CRC by modulating ETV1 and MAPK pathway. |
