Extracellular matrix and integrin signalling: the shape of things to come

Abstract

The extracellular matrix (ECM) and integrins collaborate to regulate gene expression associated with cell growth, differentiation and survival. Biochemical and molecular analyses of integrin signalling pathways have uncovered several critical cytoplasmic proteins that link the ECM and integrins to intracellular pathways that may contribute to anchorage-dependent growth. A large body of evidence now indicates that the non-receptor protein kinases focal adhesion kinase (FAK) and specific members of the mitogen-activated protein kinases (MAPKs), including the extracellular-signal-regulated kinases (ERKs), mediate these ECM- and integrin-derived signalling events. However, little is known about how FAK and MAPKs contribute to biological processes other than cell proliferation or migration. In addition, remarkably little is known concerning the signalling events that occur in cells that adhere to complex multivalent extracellular matrices via multiple integrin receptors. Given the stringent requirement for attaining a proper morphology in ECM/integrin-directed cell behaviour, it is still not clear how cell shape and tissue architecture impact upon intracellular signalling programmes involving FAK and MAPKs. However, the recent discovery that members of the Rho family of small GTPases are able to regulate ECM/integrin pathways that modulate both cell shape and intracellular signalling provides new insights into how cell morphology and signal transduction become integrated, especially within three-dimensional differentiated tissues.

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

“…Periostin is a member of a subset of secreted ECM-associated molecules termed "matri-cellular" proteins [48][49][50] that modulate interactions with structural components of the ECM, such as collagens, and a variety of cell surface receptors, such as integrins, to regulate cellular differentiation in development [51] and connective tissue disease [52]. Based on these data and numerous studies demonstrating that the ECM can potently regulate cellular differentiation [53][54][55][56][57], where possible we incorporated our periostin treatments into the collagen substrate, rather than simply amending the tissue culture media, to more closely replicate in vivo conditions. Periostin has been shown to promote collagen fibrillogenesis and alter the deposition of ECM proteins in other systems [58] and larger scale microarray studies have identified COL1A1 mRNA, encoding the collagen α1 component of heterotrimeric and homotrimeric type-1 collagen [59], as up-regulated in DD cord [11,12].…”

Synthetic Multivalent Ligands as Probes of Signal Transduction

“…Integrins can facilitate cell adhesion to extracellular matrix components as well as other cells. [185,196] The extracellular matrix, a naturally occurring multivalent display, may therefore also influence integrin activity. [197] In one study, surfaces were modified with peptide REs of different valencies for use in cell adhesion studies.…”

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

“…One of the major transducers of ECM/integrinderived signals is the focal adhesion kinase (FAK), a 125-kDa nonreceptor tyrosine kinase that can bind to, and phosphorylate, a number of intracellular signaling molecules, including Src, paxillin and p130cas, and mediate downstream activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling through a network of adaptor proteins (reviewed in Boudreau andJones, 1999 andSastry andBurridge, 2000). Increased FAK expression and/or activation have been documented in various malignancies and shown to correlate with the invasive/metastatic phenotypes of the cells (reviewed in Gabarra-Niecko et al, 2003 andKahana et al, 2002).…”