Inhibition of human breast cancer Matrigel invasion by Streptolysin O activation of the EGF receptor ErbB1
Autor: | Volkan Gurel, Albert E. Dahlberg, John Mcmichael, Emily H. Hall, David L. Brautigan |
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Rok vydání: | 2011 |
Předmět: |
genetic structures
MAP Kinase Signaling System Gene Expression Breast Neoplasms Biology Article Bacterial Proteins Cell Movement Epidermal growth factor Cell Line Tumor Humans Neoplasm Invasiveness Epidermal growth factor receptor Neoplasm Metastasis Phosphorylation Protein kinase B Matrigel Epidermal Growth Factor Kinase Cell growth Cell Biology eye diseases ErbB Receptors Drug Combinations Gene Knockdown Techniques Streptolysins Cancer cell Cancer research biology.protein Female Proteoglycans RNA Interference Streptolysin Collagen Laminin sense organs Cell Migration Assays Genes Neoplasm |
Zdroj: | Cellular Signalling. 23:1972-1977 |
ISSN: | 0898-6568 |
Popis: | Streptolysin O (SLO) is a protein cytotoxin derived from Group A beta-hemolytic streptococci that associates with membranes and permeabilizes cells. Oxidation inactivates SLO, eliminating the characteristic hemolytic and cytotoxic activities. However, oxidized SLO produces beneficial therapeutic effects in vivo on scleroderma, scar formation and wound healing. Here we report that oxidized SLO also significantly inhibited invasion by human metastatic breast cancer MDA-MB-231 cells through Matrigel in an in vitro model of metastatic disease. This dose-dependent response corresponded to selective SLO activation of epidermal growth factor receptor (EGFR) ErbB1. SLO and EGF were equally selective in activation of EGFR, but EGF elicited larger relative increases in phosphorylation at various sites, especially pronounced for Tyr845. Addition of SLO did not affect either ERK1/2 or Akt kinases and altered the expression of only 10 of 84 metastasis-related genes in MDA-MB-231 cells. Neither SLO nor EGF promoted growth of several human breast cancer cell lines. Knockdown of EGFR by siRNA ablated the inhibitory effect of SLO on cancer cell invasion, showing SLO selectively activated ErbB1 kinase to reduce invasion without increasing cell growth. The results suggest SLO might have promise as a new therapy to inhibit metastasis. |
Databáze: | OpenAIRE |
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