Overexpressed GRP78 affects EMT and cell-matrix adhesion via autocrine TGF-β/Smad2/3 signaling.
Glucose-regulated protein of 78kD (GRP78) is a multifunctional protein belonging to the heat shock protein 70 family. Overexpression of GRP78 triggered by environmental and physiological stresses is positively correlated with the occurrence and progression of various tumors, but the molecular mechanisms have not been well established. The present study indicated that overexpression of GRP78 in colon cancer cells could promote cell-matrix adhesion through the upregulation of fibronectin, integrin-β1 and phosphorylated FAK. Meanwhile, it resulted in a visible epithelial-mesenchymal transition in DLD1 cells, and the Snail-2 played the key role during the process. More importantly, the data indicated that GRP78 overexpression facilitated the expression and secretion of TGF-β1, which further activated the downstream Smad2/3 signaling module to effectuate the cell-matrix adhesion and epithelial-mesenchymal transition. Taken together, this study provides a novel molecular mechanism involving in the effects of GRP78 on colon cancer metastasis.
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
Lichao
L
Zhang
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
Zongwei
Z
Li
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Yongsheng
Y
Fan
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
Hanqing
H
Li
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: lzy@sxu.edu.cn.
Zhouyu
Z
Li
Shanxi Tumor Hospital, Taiyuan 030006, China.
Yaoping
Y
Li
D019898:Autocrine Communication; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
Cell-matrix adhesion; Epithelial–mesenchymal transition; Glucose-regulated protein 78; Snail-2; TGF-β1