Faculty Collaboration Database

Nogo-B receptor promotes epithelial-mesenchymal transition in non-small cell lung cancer cells through the Ras/ERK/Snail1 pathway. Cancer Lett 2018 Apr 01;418:135-146

Date

01/15/2018

Pubmed ID

29331415

Pubmed Central ID

PMC7385903

DOI

10.1016/j.canlet.2018.01.030

Scopus ID

2-s2.0-85041278911 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane translocation and activation of Ras in breast cancer cells and enhances the chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the role of NgBR in lung cancer has not yet been elucidated. In the present study, we found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells in vivo. In contrast, NgBR overexpression promoted EMT in and lung metastasis of NSCLC cells. At the molecular level, NgBR modulated the expression of EMT-related proteins and enhanced the protein expression of Snail1, a crucial transcription factor that represses epithelial cell protein marker E-cadherin. Moreover, we found that NgBR overexpression promoted the membrane localization of Ras and activation of downstream MEK/ERK signaling pathway and that NgBR knockdown by using a specific shRNA inversely affected the expression of EMT-related proteins in NSCLC cells. Thus, our results provide novel insights on the regulatory role of NgBR in the metastasis of NSCLC that should be investigated further for developing a therapeutic strategy for treating patients with NSCLC.

Author List

Wu D, Zhao B, Qi X, Peng F, Fu H, Chi X, Miao QR, Shao S

Author

Xiao-Mei Qi MD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

A549 Cells
Animals
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Extracellular Signal-Regulated MAP Kinases
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
Male
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
RNA Interference
Receptors, Cell Surface
Signal Transduction
Snail Family Transcription Factors
Transplantation, Heterologous
ras Proteins