scholarly journals HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion

2005 ◽  
Vol 16 (2) ◽  
pp. 550-561 ◽  
Author(s):  
Hanane Khoury ◽  
Monica A. Naujokas ◽  
Dongmei Zuo ◽  
Veena Sangwan ◽  
Melanie M. Frigault ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Invasion ◽  
Single Cells ◽  
Epithelial Morphogenesis ◽  
Cell Junctions ◽  
Junction Protein ◽  
Hepatocyte Growth ◽  
E Cadherin ◽  
Cell Cell

Activation of the hepatocyte growth factor receptor Met induces a morphogenic response and stimulates the formation of branching tubules by Madin-Darby canine kidney (MDCK) epithelial cells in three-dimensional cultures. A constitutively activated ErbB2/Neu receptor, NeuNT, promotes a similar invasive morphogenic program in MDCK cells. Because both receptors are expressed in breast epithelia, are associated with poor prognosis, and hepatocyte growth factor (HGF) is expressed in stroma, we examined the consequence of cooperation between these signals. We show that HGF disrupts NeuNT-induced epithelial morphogenesis, stimulating the breakdown of cell-cell junctions, dispersal, and invasion of single cells. This correlates with a decrease in junctional proteins claudin-1 and E-cadherin, in addition to the internalization of the tight junction protein ZO-1. HGF-induced invasion of NT-expressing cells is abrogated by pretreatment with a pharmacological inhibitor of the mitogen-activated protein kinase kinase (MEK) pathway, which restores E-cadherin and ZO-1 at cell-cell junctions, establishing the involvement of MEK-dependent pathways in this process. These results demonstrate that physiological signals downstream from the HGF/Met receptor synergize with ErbB2/Neu to enhance the malignant phenotype, promoting the breakdown of cell-cell junctions and enhanced cell invasion. This is particularly important for cancers where ErbB2/Neu is overexpressed and HGF is a physiological growth factor found in the stroma.

Effects of hepatocyte growth factor on E-cadherin-mediated cell-cell adhesion in DU145 prostate cancer cells

Urology ◽  
2001 ◽  
Vol 58 (6) ◽  
pp. 1064-1069 ◽  
Author(s):  
Hidenobu Miura ◽  
Kenji Nishimura ◽  
Akira Tsujimura ◽  
Kiyomi Matsumiya ◽  
Kunio Matsumoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Hepatocyte Growth ◽  
E Cadherin ◽  
Cell Cell

scholarly journals Cancer Cell Invasion in Three-dimensional Collagen Is Regulated Differentially by Gα13 Protein and Discoidin Domain Receptor 1-Par3 Protein Signaling

2015 ◽  
Vol 291 (4) ◽  
pp. 1605-1618 ◽  
Author(s):  
Christina R. Chow ◽  
Kazumi Ebine ◽  
Lawrence M. Knab ◽  
David J. Bentrem ◽  
Krishan Kumar ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Invasion ◽  
Single Cells ◽  
Three Dimensional ◽  
Cell Junctions ◽  
Membrane Type ◽  
Discoidin Domain Receptor 1 ◽  
E Cadherin ◽  
Cell Cell

Cancer cells can invade in three-dimensional collagen as single cells or as a cohesive group of cells that require coordination of cell-cell junctions and the actin cytoskeleton. To examine the role of Gα13, a G12 family heterotrimeric G protein, in regulating cellular invasion in three-dimensional collagen, we established a novel method to track cell invasion by membrane type 1 matrix metalloproteinase-expressing cancer cells. We show that knockdown of Gα13 decreased membrane type 1 matrix metalloproteinase-driven proteolytic invasion in three-dimensional collagen and enhanced E-cadherin-mediated cell-cell adhesion. E-cadherin knockdown reversed Gα13 siRNA-induced cell-cell adhesion but failed to reverse the effect of Gα13 siRNA on proteolytic invasion. Instead, concurrent knockdown of E-cadherin and Gα13 led to an increased number of single cells rather than groups of cells. Significantly, knockdown of discoidin domain receptor 1 (DDR1), a collagen-binding protein that also co-localizes to cell-cell junctions, reversed the effects of Gα13 knockdown on cell-cell adhesion and proteolytic invasion in three-dimensional collagen. Knockdown of the polarity protein Par3, which can function downstream of DDR1, also reversed the effects of Gα13 knockdown on cell-cell adhesion and proteolytic invasion in three-dimensional collagen. Overall, we show that Gα13 and DDR1-Par3 differentially regulate cell-cell junctions and the actin cytoskeleton to mediate invasion in three-dimensional collagen.

scholarly journals Hepatocyte Growth Factor/Met System Promotes Endometrial and Endometriotic Stromal Cell Invasion via Autocrine and Paracrine Pathways

2004 ◽  
Vol 89 (2) ◽  
pp. 823-832 ◽  
Author(s):  
Souichi Yoshida ◽  
Tasuku Harada ◽  
Masahiro Mitsunari ◽  
Tomio Iwabe ◽  
Yasuko Sakamoto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Invasion ◽  
Stromal Cell ◽  
Hepatocyte Growth

Effect of Geldanamycin on the Glioma Cell Invasion Induced by Hepatocyte Growth Factor

2014 ◽  
Vol 1033-1034 ◽  
pp. 224-228
Author(s):  
Yan Xia Sun ◽  
Guang Yu Zhou ◽  
Li Li ◽  
Xue Mei Han
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Invasion ◽  
Culture System ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Glioma Cell Line ◽  
Invasive Growth ◽  
Transwell Culture ◽  
Hepatocyte Growth

To investigate the effect of geldanamycin (GDM) on the invasion ability of glioma cell induced by hepatocyte growth factor (HGF). Malignant glioma cell line U251-MG and U87-MG were cultured’and the capability of cell invasion was detected using a Transwell culture system. HGF significantly promoted the invasion ability of both U251-MG and U87-MG cells as compared with the normal control (NC) (P < 0.05). Forty eight hours after GDM treatment, the invasive growth of glioma cells was significantly decreased as compared with either NC or HGF group (P < 0.05). When cells were exposed to GDM plus HGF for 48 h, the cell invasion capability was greatly reduced as compared with either NC or HGF group (P < 0.05). The number of invaded cells in GDM plus HGF group was similar to that of GDM group.GDM can inhibit the invasion ability of glioma cells induced by HGF.

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