Extracellular matrix-Induced gene expression in human breast cancer cells

Nandor Garamszegi, Susanna P. Garamszegi, Lina A. Shehadeh, Sean P. Scully

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Extracellular matrix (ECM) molecules modify gene expression through attachment-dependent (focal adhesion-related) integrin receptor signaling. It was previously unknown whether the same molecules acting as soluble peptides could generate signal cascades without the associated mechanical anchoring, a condition that may be encountered during matrix remodeling and degradation and relevant to invasion and metastatic processes. In the current study, the role of ECM ligand-regulated gene expression through this attachment-independent process was examined. It was observed that fibronectin, laminin, and collagen type I and II induce Smad2 activation in MCF-10A and MCF-7 cells. This activation is not caused by transforming growth factor (TGF)-β ligand contamination or autocrine TGF involvement and is 3- to 5-fold less robust than the TGF-pl ligand. The resulting nuclear translocation of Smad4 in response to ECM ligand indicates downstream transcriptional responses occurring. Coimmunoprecipitation experiments determined that collagen type II and laminin act through interaction with integrin α 2β 1 receptor complex. The ECM ligand-induced Smad activation (termed signaling crosstalk) resulted in cell type and ligand-specific transcriptional changes, which are distinct from the TGF- i ligand-induced responses. These findings show that cell-matrix communication is more complex than previously thought. Soluble ECM peptides drive transcriptional regulation through corresponding adhesion and non-attachment-related processes. The resultant gene expressional patterns correlate with pathway activity and not by the extent of Smad activation. These results extend the complexity and the existing paradigms of ECM-cell communication to ECM ligand regulation without the necessity of mechanical coupling.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
JournalMolecular Cancer Research
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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