The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration

Hamelers, Irene H.L.; Olivo, Cristina; Mertens, Alexander E.E.; Pegtel, D. Michiel; Kammen, Rob A. van der; Sonnenberg, Arnoud; Collard, John G.

doi:10.1083/jcb.200509172

Cited by 85 publications

(78 citation statements)

References 51 publications

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“…Rap1 is a potent activator of integrins and has been shown to induce cell polarization, cell surface receptor redistribution, and migration (3,32,37,38). Rac1 is important for actin reorganization and cell protrusion (39)(40)(41)(42)(43). Ras has been shown to be important for TCR signaling pathways essential for cell proliferation, e.g., ERK and JNK (33,34).…”

Section: Discussionmentioning

confidence: 99%

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Fischer

Jacovetty

Medeiros

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The role continuous contact with self-peptide/MHC molecules (self ligands) in the periphery plays in the function of mature T cells remains unclear. Here, we elucidate a role for MHC class II molecules in T cell trafficking and antigen responsiveness in vivo. We find that naïve CD4 T cells deprived of MHC class II molecules demonstrate a progressive and profound defect in motility (measured by real-time two-photon imaging) and that these cells have a decreased ability to interact with limiting numbers of cognate antigen-bearing dendritic cells, but they do not demonstrate a defect in their responsiveness to direct stimulation with anti-CD3 monoclonal antibody. Using GST fusion proteins, we show that MHC class II availability promotes basal activation of Rap1 and Rac1 but does not alter the basal activity of Ras. We propose that tonic T cell receptor signaling from self-ligand stimulation is required to maintain a basal state of activation of small guanosine triphosphatases critical for normal T cell motility and that T cell motility is critical for the antigen receptivity of naïve CD4 T cells. These studies suggest a role for continuous self-ligand stimulation in the periphery for the maintenance and function of mature naïve CD4 T cells.GTPases ͉ MHC class II deficiency ͉ self ligand

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Section: Discussionmentioning

confidence: 99%

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Fischer

Jacovetty

Medeiros

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…As shown in Figure 5B and C, the migration could be inhibited by NSC23766 in both LnCap and Du145 cells ( Figure 5B and C). To further confirm the effect of Rac1 on Cyr61-induced cell migration, we transfected the Du145/Cyr61i cells with T-cell lymphoma invasion and metastasis 1 (Tiam1), which was reported as a specific activator of Rac1 (Hamelers et al, 2005;Cruz-Monserrate and O'Connor, 2008). Tiam1-transfected Du145/Cyr61i cells effectively reversed the migration-suppression effects of Cyr61 silencing ( Figure 5D).…”

Section: Effect Of Cyr61 On Pca Cell Migration Was Mediated Through Tmentioning

confidence: 99%

Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells

et al. 2008

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Cyr61 has been reported to participate in the development and progression of various cancers; however, its role in prostate cancer (PCa) still remains poorly understood. In this study, we explored the function of Cyr61 in a series of malignant PCa cell lines, including LnCap, Du145, and PC3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays demonstrated that Cyr61 was essential for the proliferation of PCa cells. Soft agar assay and xenograft analysis showed that downregulation of Cyr61 suppressed the tumorigenicity of Du145 cells both in vitro and in vivo. Either silencing the cellular Cyr61 by RNA interference or neutralising the endogenous Cyr61 by antibody inhibited the migration of Du145 cells. In contrast, purified protein of Cyr61 promoted the migration of LnCap cells in a dose-dependent manner. These results suggested that Cyr61 was involved in the migration of PCa cells. We also observed the accumulation of mature focal adhesion complexes associated with the impaired migration through Cyr61 downregulation. Also, further studies showed that Cyr61 regulated the level of activated Rac1 as well as its downstream targets, including phosphorylated JNK, E-cadherin, and p27 kip1 , which are key molecules involved in cell growth, migration, and invasion. The in vivo mouse tail vein injection experiment revealed that Cyr61 affected the metastatic capacity of Du145 cells, suggesting that Cyr61 was required for prostate tumour metastasis. Altogether, our results demonstrated that Cyr61 played an important role in the tumorigenicity and metastasis of PCa cells, which will benefit the development of therapeutic strategy for PCas.

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“…α3β1 integrin signaling is also involved in laminin-332 matrix assembly by normal and tumor cells [87,88]. This appears to involve Rho-GTPases, stress fiber and focal contact formation and is dependent on the protein T-lymphoma invasion and metastasis 1 (Tiam1) [87,88].…”

Section: Section 2 Part 3: Laminin-332 Signal Transduction In Cancermentioning

confidence: 99%

Laminin-332-Integrin Interaction: A Target For Cancer Therapy?

Tsuruta

Kobayashi²,

Imanishi³

et al. 2008

CMC

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For many years, extracellular matrix (ECM) was considered to function as a tissue support and filler. However, we now know that ECM proteins control many cellular events through their interaction with cell-surface receptors and cytoplasmic signaling pathways. For example, they regulate cell proliferation, cell division, cell adhesion, cell migration, and apoptosis. We focus in this review on a laminin isoform, laminin-332 (formerly termed laminin-5), a major component of the basement membrane (BM) of skin and other epithelial tissues. It is composed of 3 subunits (α3, β3, and γ2) and interacts with at least two integrin receptors expressed by epithelial cells (α3β1 and α6β4 integrin). Mutations in either laminin-332 or integrin α6β4 result in junctional epidermolysis bullosa, a blistering skin disease, while targeting of laminin-332 by autoantibodies in cicatricial pemphigoid leads to dysadhesion of epithelial cells from their underlying connective tissue. Abnormal expression of laminin-332 and its integrin receptors is also a hallmark of certain tumor types and is believed to promote invasion of colon, breast and skin cancer cells. Moreover, there is emerging evidence that laminin-332 and its protease degradation products are not only found at the leading front of several tumors but also likely induce and/or promote tumor cell migration. Thus, in this review, we focus specifically on the role of laminin-332 and its integrin receptors in adhesion, proliferation, and migration/invasion of cancer cells. Finally, we discuss strategies for the development of laminin-332-based antagonists for the treatment of malignant tumors.

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The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration

Cited by 85 publications

References 51 publications

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells

Laminin-332-Integrin Interaction: A Target For Cancer Therapy?

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