Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers

Saoncella, Stefania; Echtermeyer, Frank; Denhez, Fabienne; Nowlen, Julie; Mosher, Deane F.; Robinson, Stephen D.; Hynes, Richard O.; Goetinck, Paul F.

doi:10.1073/pnas.96.6.2805

Cited by 342 publications

(342 citation statements)

References 35 publications

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“…2, top right panel). FN−/− cells, which were derived from embryonic stem cells from a FN-knock-out mouse (George et al, 1993) and selected based on their fibroblastic character, have been demonstrated not to secrete FN (Saoncella et al, 1999). In addition, we detected no FN in cell layers with rabbit anti-human 70K antibodies that recognize mouse FN (Fig.…”

Section: K Binds To Cells In Linear Arrays In the Absence Of Intact Fnmentioning

confidence: 65%

“…FN−/− and FN+/− mouse fibroblasts had been derived from FN−/− and FN+/− embryonic stem cells obtained from homozygous and heterozygote FN knock-out mice (George et al, 1993;Saoncella et al, 1999). Cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Life Technologies, Inc.) with 10% fetal bovine serum (Intergen, Purchase, NY) and 100 IU/ ml penicillin and 100 μg/ml streptomycin.…”

Section: Cell Culturementioning

confidence: 99%

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The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin assembly sites in the absence of intact fibronectin

2006

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Binding of the N-terminal 70-kDa (70K) fragment of fibronectin to fibroblasts blocks assembly of intact fibronectin and is an accurate indicator of the ability of various agents to enhance or inhibit fibronectin assembly. Such binding is widely thought to be to already assembled fibronectin. We evaluated this hypothesis with fibronectin-null mouse fibroblasts plated on laminin-1 in the absence of intact fibronectin. As a proteolytic fragment or recombinant protein, 70K bound fibronectin-null cells specifically in linear arrays that extended outwards from the periphery of spread cells. At early time points, these arrays were similar to those formed by intact fibronectin. 70K arrays formed within 5min following ligand addition at concentrations as low as 5nM, indicating rapid and high affinity binding. Bound 70K was extractable with Triton X-100 or deoxycholate but became insoluble when cross-linked with a membrane-impermeable agent into large SDS-stable complexes. Intact fibronectin, in contrast, became progressively non-extractable in the absence of cross-linking. The detergent-resistant arrays of cross-linked 70K localized to tips of cellular extensions and partially overlapped with α 6 and β 1 integrin subunits at the base of the extensions. α 5 did not localize with 70K arrays, but became progressively co-localized with assemblies of intact fibronectin over time. These results support a model in which the 70-kDa region of fibronectin binds to linearly arrayed cell surface molecules of adherent cells to initiate assembly, display of the arrays is controlled by the integrin that mediates adhesion, and fibronectin-binding integrins promote fibronectinfibronectin interactions during progression of assembly.

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Section: K Binds To Cells In Linear Arrays In the Absence Of Intact Fnmentioning

confidence: 65%

Section: Cell Culturementioning

confidence: 99%

The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin assembly sites in the absence of intact fibronectin

2006

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“…Regulation through phosphorylation of syndecan-4 cytoplasmic tail may also exist in syndecan-4 signaling (Horowitz et al, 1999). The involvement of Rho activity in the formation FAs and stress fibers through syndecan-4 signaling has also been suggested (Saoncella et al, 1999;Couchman et al, 2001). Besides all signaling molecules described above, stretch-activated ion channels are considered to be candidates for mechanotransduction mechanisms (Hu and Sachs, 1997;Sadoshima and Izumo, 1997).…”

Section: Cellular Mechanotransductionmentioning

confidence: 99%

“…Syndecan-4 is involved in cytoskeletal reorganization, assembly of stress fibers, and FA formation. In fact, it has been shown to be required for FA formation in addition to integrins (Saoncella et al, 1999;Woods et al, 2000). Recruitment of syndecan-4 to FAs is dependent on PKC activation, and multimerization of the cytoplasmic domain of syndecan-4 is required for kinase binding and activation (Baciu and Goetinck, 1995).…”

Section: Cellular Mechanotransductionmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

219

186

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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“…Concomitant engagement of Sdc4 and integrins promotes Rho GTPase and focal adhesion kinase (FAK) activities, which are crucial for efficient initiation of FN matrix assembly. [12][13][14][15] Sdc1 is expressed primarily by epithelial and plasma cells of healthy adult tissue. 16 Recently, we and others 17,18 observed the induction of Sdc1 in stromal fibroblasts of invasive breast carcinomas.…”

mentioning

confidence: 99%

Syndecan-1 in Breast Cancer Stroma Fibroblasts Regulates Extracellular Matrix Fiber Organization and Carcinoma Cell Motility

Yang

Mosher

Seo

et al. 2011

The American Journal of Pathology

121

126

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Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion. Epithelial-stromal interactions play crucial roles in directing mammary gland development and in maintaining normal tissue homeostasis. Conversely, during tumorigenesis, the stroma accelerates carcinoma growth and progression. The predominant cell type within the stromal compartment is the fibroblast, which synthesizes, organizes, and maintains a three-dimensional (3D) network of glycoproteins and proteoglycans known as the extracellular matrix (ECM). Normal stromal fibroblasts and their ECM are believed to exert an inhibitory constraint on tumor growth and progression. 1,2 Major alterations occur in the stromal fibroblasts and ECM during neoplastic transformation, giving rise to a permissive and supportive microenvironment for carcinomas. Compared with their quiescent normal counterpart, carcinoma-associated fibroblasts display an activated phenotype, which is characterized by the expression of smooth muscle markers, an enhanced proliferative and migratory potential, and altered gene expression profiles. Carcinoma-associated fibroblasts produce and deposit elevated amounts and abnormal varieties of ECM components. 3-5 Recent evidence 6,7 indicates that not only ECM composition but also ECM architecture are altered in carcinomas and that these changes may promote tumor progression. However, the contribution of these stromal modifications to tumor development and the molecular mechanisms and signaling events underlying these alterations are incompletely understood.

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Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers

Cited by 342 publications

References 35 publications

The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin assembly sites in the absence of intact fibronectin

The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin assembly sites in the absence of intact fibronectin

Mechanoregulation of gene expression in fibroblasts

Syndecan-1 in Breast Cancer Stroma Fibroblasts Regulates Extracellular Matrix Fiber Organization and Carcinoma Cell Motility

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