Overexpression of c-Src Enhances Cell-Matrix Adhesion and Cell Migration in PDGF-Stimulated NIH3T3 Fibroblasts

Verbeek, Bianca S.; Vroom, Thea M.; Rijksen, Gert

doi:10.1006/excr.1999.4416

Cited by 21 publications

(17 citation statements)

References 35 publications

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“…9). It was also supported by the findings that tyrosine containing the proteins c-Src (Rohrschneider, 1980) and p130Cas (Harte et al, 1996) participate in focal-adhesion complexes and are essential proteins in cell migration (Klemke et al, 1998;Rahimi et al, 1998;Verbeek et al, 1999). Furthermore, our present findings indicate that Src kinase activity and Cas tyrosine phosphorylation were important for their colocalization at focal adhesion because Ang II-stimulated colocalization did not occur in both KI Src-and ⌬SD Cas-overexpressed cells (Fig.…”

Section: Src and Cas In Ang Ii-stimulated Vsmc Migration 839supporting

confidence: 87%

“…These results suggest that Src and Cas are critically required for Ang II-stimulated migration of RASMC. It was also reported that Src activity was required for the migration of a number of cell types (Rahimi et al, 1998;Verbeek et al, 1999). Klemke et al (1998) also reported that Cas/Crk coupling serves as a "molecular switch" for the induction of cell migration.…”

Section: Src and Cas In Ang Ii-stimulated Vsmc Migration 839mentioning

confidence: 96%

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Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation

et al. 2004

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Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang IIstimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (⌬SD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2Ј-amino-3Ј-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src-and ⌬SD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth (Berk et al., 1989) and migration (Griendling et al., 1996), such as atherosclerosis, restenosis after angioplasty, and hypertension. It was indicated that tyrosine phosphorylation is a critical episode in several Ang II-stimulated signaling events (Marrero et al., 1996). Ang II induces tyrosine phosphorylation of proteins with apparent molecular masses of 42, 44, 70 to 80, 110 to 130, and 190 kDa in VSMC (Tsuda et al., 1991). The 130-, 60-, 44-, and 42-kDa proteins that were tyrosine-phosphorylated in response to Ang II in VSMC were identified as p130Cas [a CT-10 -regulated kinase (Crk)-associated substrate] (Takahashi et al., 1998), 60-kDa c-Src, a nonreceptor tyrosine kinase (Ishida et al., 1995), and mitogen-activated protein (MAP) kinase isozymes (Tsuda et al., 1992), respectively.Cell migration requires cytoskeletal reorganization involving phosphorylation of cytoskeleton-associated tyrosine kinases and formation of focal-adhesion complexes (Ilic et al.,

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Section: Src and Cas In Ang Ii-stimulated Vsmc Migration 839supporting

confidence: 87%

Section: Src and Cas In Ang Ii-stimulated Vsmc Migration 839mentioning

confidence: 96%

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation

et al. 2004

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“…logically abnormal focal adhesions and are defective in cell substrate adhesion (55). RAFTK, which is a novel member of the focal adhesion kinase family, acts as a "platform kinase" and links chemokine receptors to the nucleus via the MAP kinase pathway and cytoskeleton in blood cells (40).…”

Section: Discussionmentioning

confidence: 99%

Slit Protein-mediated Inhibition of CXCR4-induced Chemotactic and Chemoinvasive Signaling Pathways in Breast Cancer Cells

Prasad

Fernandis

Rao

et al. 2004

Journal of Biological Chemistry

117

115

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Slit, which mediates its function by binding to the Roundabout (Robo) receptor, has been shown to regulate neuronal and CXCR4-mediated leukocyte migration. Slit-2 was shown to be frequently inactivated in lung and breast cancers because of hypermethylation of its promoter region. Furthermore, the CXCR4/CXCL12 axis has been reported recently to be actively involved in breast cancer metastasis to target organs such as lymph nodes, lung, and bone. In this study, we sought to characterize the effect of Slit (‫؍‬Slit-2) on the CXCL12/ CXCR4-mediated metastatic properties of breast cancer cells. We demonstrate here that breast cancer cells and tissues derived from breast cancer patients express Robo 1 and 2 receptors. We also show that Slit treatment inhibits CXCL12/CXCR4-induced breast cancer cell chemotaxis, chemoinvasion, and adhesion, the fundamental components that promote metastasis. Slit had no significant effect on the CXCL12-induced internalization process of CXCR4. In addition, characterization of signaling events revealed that Slit inhibits CXCL12-induced tyrosine phosphorylation of focal adhesion components such as RAFTK/Pyk2 at residues 580 and 881, focal adhesion kinase at residue 576, and paxillin. We found that Slit also inhibits CXCL12-induced phosphatidylinositol 3-kinase, p44/42 MAP kinase, and metalloproteinase 2 and 9 activities. However, it showed no effect on JNK and p38 MAP kinase activities. To our knowledge, this is the first report to analyze in detail the effect of Slit on breast cancer cell motility as well as its effect on the critical components of the cancer cell chemotactic machinery. Studies of the Slit-Robo complex may foster new anti-chemotactic approaches to block cancer cell metastasis.

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“…79,81,82 For example, Src can synergize with EGFR to promote cell proliferation, 83 as well as the PDGFR to induce integrindependent cell adhesion and migration. 84 Knockout mice lacking individual or combinations of multiple SFKs have provided an important physiological basis for mechanisms of compensation among related SFKs using traditional knockout mouse strategies. 85 Although the capacity for SFKs to support compensation in the absence of another SFK(s) has been previously reviewed, 86 recent emerging evidence suggests that there may be additional functions of SFKs that are physiologically important during pathological disease.…”

Section: Analysis Of Integrin and Growth Factor Signaling Crosstalk Imentioning

confidence: 99%

Integrin and Growth Factor Receptor Crosstalk

Eliceiri

2001

Circulation Research

356

294

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Abstract-Crosstalk between integrins and growth factor receptors are an important signaling mechanism to provide specificity during normal development and pathological processes in vascular biology. Evidence from several model systems demonstrates the physiological importance of the coordination of signals from growth factors and the extracellular matrix to support cell proliferation, migration, and invasion in vivo. Several examples of crosstalk between these two important classes of receptors indicate that integrin ligation is required for growth factor-induced biological processes. Furthermore, integrins can directly associate with growth factor receptors, thereby regulating the capacity of integrin/growth factor receptor complexes to propagate downstream signaling. Recent data suggest that antagonists of ␣ v integrins can provide a therapeutic benefit in human cancer patients, whereas knockout mice lacking specific integrins can provide an interesting insight into the role of integrins during development. This review will focus on the biological importance of integrin and growth factor receptor crosstalk that occurs during cell growth, migration, and invasion as well as in endothelial cells during angiogenesis. Key Words: integrins Ⅲ growth factor receptors Ⅲ cell migration/invasion Ⅲ angiogenesis R ecent work from a number of laboratories has demonstrated that cell adhesion receptors and growth factor receptors are important molecular determinants in providing specificity for signaling during development and/or during pathological processes. Although integrins and growth factor receptors can independently propagate intracellular signals, the synergy of signals provided by the extracellular matrix (ECM) and growth factors appears to regulate complex processes, including blood vessel development during embryogenesis as well as tumor growth/metastasis and angiogenesis in the adult. Analysis of the crosstalk between the biochemical pathways mediated by integrins and growth factor receptors may ultimately lead to a better understanding of the cell biological processes underlying normal development and the progression of pathological conditions. Several excellent reviews on integrin-mediated 1-4 and growth factor receptormediated signal transduction 5,6 have been recently published; therefore, this review will focus on the evidence for crosstalk between integrins and growth factor receptors in cell biology. These in vitro studies help provide an important insight into the role of integrins in more complex biological questions in vascular biology. This will be followed by an analysis of the recent progress on growth factor-induced angiogenesis as a paradigm for the study of the crosstalk between growth factor receptors and integrins in intact tissues. Recent work provides clinical data on the therapeutic benefit of ␣ v integrin antagonists, whereas studies of knockout mice, lacking various integrins, provide insight into the role of integrins during the embryonic development of the mouse vasculature. Model systems...

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Overexpression of c-Src Enhances Cell-Matrix Adhesion and Cell Migration in PDGF-Stimulated NIH3T3 Fibroblasts

Cited by 21 publications

References 35 publications

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation

Slit Protein-mediated Inhibition of CXCR4-induced Chemotactic and Chemoinvasive Signaling Pathways in Breast Cancer Cells

Integrin and Growth Factor Receptor Crosstalk

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Overexpression of c-Src Enhances Cell-Matrix Adhesion and Cell Migration in PDGF-Stimulated NIH3T3 Fibroblasts

Cited by 21 publications

References 35 publications

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-Terminal Kinase Activation

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-Terminal Kinase Activation

Slit Protein-mediated Inhibition of CXCR4-induced Chemotactic and Chemoinvasive Signaling Pathways in Breast Cancer Cells

Integrin and Growth Factor Receptor Crosstalk

Contact Info

Product

Resources

About

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase Activation