1. Glucose-Regulated Protein 94 Mediates the Proliferation and Metastasis through the Regulation of ETV1 and MAPK Pathway in Colorectal Cancer
- Author
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Po Li Wei, Chien Yu Huang, Uyanga Batzorig, Weu Wang, and Yu Jia Chang
- Subjects
Male ,MAPK/ERK pathway ,Epithelial-Mesenchymal Transition ,Carcinogenesis ,MAP Kinase Signaling System ,Glucose-regulated protein ,proliferation ,p38 mitogen-activated protein kinases ,colorectal cancer ,GRP94 ,metastasis ,medicine.disease_cause ,ETV1 ,Metastasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cell Proliferation ,Gene knockdown ,Membrane Glycoproteins ,biology ,Cell growth ,General Medicine ,medicine.disease ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Gene Knockdown Techniques ,Cancer research ,biology.protein ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,Transcription Factors ,Research Paper - Abstract
Colorectal cancer (CRC) is a worldwide health problem. Glucose-regulated protein 94 (GRP94) is known as an important endoplasmic reticulum-stress response protein that shows correlation with aggressive cancer behavior. However, the role of GRP94 in CRC is still unclear. Our results showed that silencing GRP94 (GRP94-KD) reduced cell proliferation, invasion and migration of CRC cells and suppressed tumorigenesis in the xenograft mouse model. Rescue assay showed that ETV1 overexpression reversed the effect of GRP94 on cell proliferation and migration. In the molecular mechanism, we found that knockdown of GRP94 inhibited the level of MAPK pathway, including ERK/p-ERK, JNK/p-JNK, and p38/p-p38 signals. Cyclooxygenase-2 and epithelial-mesenchymal transformation biomarkers, such as N-cadherin, vimentin, and β-catenin were suppressed in GRP94 knockdown cells. Treatment of specific inhibitors of MAPK pathway showed that ERK/p-ERK, and p38/p-p38 inhibitors significantly influenced ETV1 expression as compared to JNK/p-JNK inhibitor. Our results indicated that silencing GRP94 repressed the ability of EMT process, cancer cell proliferation, metastasis, and CRC tumorigenesis. Therefore, GRP94 may play an important role in CRC by regulating ETV1 and MAPK pathway.
- Published
- 2021