Overexpressed GRP78 affects EMT and cell-matrix adhesion via autocrine TGF-β/Smad2/3 signaling. (July 2015)

• Record Type: Journal Article
• Authors: Zhang, Lichao; Li, Zongwei; Fan, Yongsheng; Li, Hanqing; Li, Zhouyu; Li, Yaoping
• Is Part Of: International journal of biochemistry & cell biology. Volume 64(2015:Jul.)
• Page Start: 202
• Page End: 211
• Publication Date: 2015-07
• Subjects: Glucose-regulated protein 78 -- Cell-matrix adhesion -- Epithelial–mesenchymal transition -- Snail-2 -- TGF-β1; GRP78 glucose-regulated protein of 78 kD -- EMT epithelial–mesenchymal transition -- MET mesenchymal–epithelial transition -- HSP heat shock protein -- ER endoplasmic reticulum -- CRC Colorectal cancer -- ECM extracellular matrix -- FAK focal adhesion kinase -- TGF-β transforming growth factor β -- TGF-β1 transforming growth factor β1 -- GFP green fluorescent protein -- uPA urokinase-type plasminogen activator -- uPAR urokinase-type plasminogen activator receptor -- α-SMA α-smooth muscle actin; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.04.012
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: GRP78 facilitates cell-ECM adhesion by induce activation of fibronectin-integrin-β1-FAK signaling pathway. GRP78 induced cell–cell dissociation and EMT. Snail-2 plays the key role in GRP78 mediated adhesion switch and EMT. GRP78 promoted the expression and secretion of TGF-β1, and activated downstream TGF-β/Smad signaling pathway. Abstract: Glucose-regulated protein of 78 kD (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.