scholarly journals Differential consequences of neurokinin receptor 1 and 2 antagonists in metastatic breast carcinoma cells; Effects independent of Substance P

2018 ◽  
Vol 108 ◽  
pp. 263-270 ◽  
Author(s):  
Esra Nizam ◽  
Nuray Erin
Keyword(s):  
Breast Carcinoma ◽  
Substance P ◽  
Metastatic Breast ◽  
Carcinoma Cells ◽  
Metastatic Breast Carcinoma ◽  
Breast Carcinoma Cells ◽  
Neurokinin Receptor

scholarly journals Integrin (α6β4) regulation of eIF-4E activity and VEGF translation

2002 ◽  
Vol 158 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Jun Chung ◽  
Robin E. Bachelder ◽  
Elizabeth A. Lipscomb ◽  
Leslie M. Shaw ◽  
Arthur M. Mercurio
Keyword(s):  
Growth Factor ◽  
Breast Carcinoma ◽  
Metastatic Breast ◽  
Carcinoma Cells ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Autocrine Signaling ◽  
Metastatic Breast Carcinoma ◽  
Translational Repressor ◽  
Breast Carcinoma Cells

We define a novel mechanism by which integrins regulate growth factor expression and the survival of carcinoma cells. Specifically, we demonstrate that the α6β4 integrin enhances vascular endothelial growth factor (VEGF) translation in breast carcinoma cells. The mechanism involves the ability of this integrin to stimulate the phosphorylation and inactivation of 4E-binding protein (4E-BP1), a translational repressor that inhibits the function of eukaryotic translation initiation factor 4E (eIF-4E). The regulation of 4E-BP1 phosphorylation by α6β4 derives from the ability of this integrin to activate the PI-3K–Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that can phosphorylate 4E-BP1. Importantly, we show that this α6β4-dependent regulation of VEGF translation plays an important role in the survival of metastatic breast carcinoma cells by sustaining a VEGF autocrine signaling pathway that involves activation of PI-3K and Akt. These findings reveal that integrin-mediated activation of PI-3K–Akt is amplified by integrin-stimulated VEGF expression and they provide a mechanism that substantiates the reported role of α6β4 in carcinoma progression.

scholarly journals Persistent Signaling by Dysregulated Thrombin Receptor Trafficking Promotes Breast Carcinoma Cell Invasion

2004 ◽  
Vol 24 (5) ◽  
pp. 1990-1999 ◽  
Author(s):  
Michelle A. Booden ◽  
Lynn B. Eckert ◽  
Channing J. Der ◽  
JoAnn Trejo
Keyword(s):  
Breast Carcinoma ◽  
Cell Invasion ◽  
Carcinoma Cell ◽  
Metastatic Breast ◽  
Normal Breast ◽  
Carcinoma Cells ◽  
Metastatic Breast Carcinoma ◽  
Extracellular Signal ◽  
Protease Activated Receptor 1 ◽  
G Protein Coupled

ABSTRACT Increased expression of protease-activated receptor 1 (PAR1), a G protein-coupled receptor for thrombin, has previously been correlated with breast carcinoma cell invasion. PAR1 is irreversibly proteolytically activated, internalized, and sorted directly to lysosomes, a critical process for the termination of signaling. We determined that activated PAR1 trafficking is severely altered in metastatic breast carcinoma cells but not in nonmetastatic or normal breast epithelial cells. Consequently, the proteolytically activated receptor is not sorted to lysosomes and degraded. Altered trafficking of proteolytically activated PAR1 caused sustained activation of phosphoinositide hydrolysis and extracellular signal-regulated kinase signaling, even after thrombin withdrawal, and enhanced cellular invasion. Thus, our results reveal that a novel alteration in trafficking of activated PAR1 causes persistent signaling and, in addition to other processes and proteins, contributes to breast carcinoma cell invasion.

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