Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

Caswell, Patrick T.; Spence, Heather J.; Parsons, Maddy; White, Dominic P.; Clark, Katherine; Cheng, Kwai Wa; Mills, Gordon B.; Humphries, Martin J.; Messent, Anthea J.; Anderson, Kurt I.; McCaffrey, Mary W.; Ozanne, Brad; Norman, Jim C.

doi:10.1016/j.devcel.2007.08.012

Cited by 371 publications

(388 citation statements)

References 41 publications

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“…Consistent with this observation, in vivo, upregulation of Ptc1 expression in response to the activation of the classical Shh signaling pathway is only observed from 18 to 24 hpe, concomitant with the effect of Shh misexpression on neural proliferation and dorsoventral patterning. A possibility is that Shh activity affects intracellular trafficking of ␤1 integrins via Rab-GTPases known to associate directly with them to favor cell migration (Caswell et al, 2007). However, blocking HH signaling pathway in zebrafish by cyclopamine induces cells to inappropriately exit the spinal cord, a phenotype reminiscent of our loss-of-function experiments (Ungos et al, 2003).…”

Section: Discussionmentioning

confidence: 95%

Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Fournier-Thibault

Blavet²,

Jarov³

et al. 2009

J. Neurosci.

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In vertebrates, the embryonic nervous system is shaped and patterned by a series of temporally and spatially regulated cell divisions, cell specifications, and cell adhesions and movements. Morphogens of the Hedgehog, Wnt, and bone morphogenetic protein families have been shown to play a crucial role in the control of cell division and specification in the trunk neural tube, but their possible implication in the regulation of adhesive events has been poorly documented. In the present study, we demonstrate that Sonic hedgehog regulates neural epithelial cell adhesion and polarity through regulation of integrin activity, cadherin cell-cell contact, and cell polarity genes in immature neural epithelial cells before the specification of neuronal cells. We propose that Sonic hedgehog orchestrates neural tube morphogenesis by coordinating adhesive and motility events with cell proliferation and differentiation.

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Section: Discussionmentioning

confidence: 95%

Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Fournier-Thibault

Blavet²,

Jarov³

et al. 2009

J. Neurosci.

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“…These results indicated that Rab25 is an oncogene-like protein that promotes tumour growth in ovarian and breast cancer models 4,5 , but acts as a tumour growth suppressor in intestinal epithelial cells, which raises the question of why the same Rab protein functions differently in different cancers. Such discrepancy was also found for hRAB37 in lung cancer and renal cell carcinoma where KD of hRAB37 reduced cell growth of renal cell carcinoma cell lines 29 .…”

Section: Article Nature Communications | Doi: 101038/ncomms5804mentioning

confidence: 99%

Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis

et al. 2014

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Rab small GTPases are master regulators of membrane trafficking and guide vesicle targeting. Recent publications show that Rab-controlled trafficking pathways are altered during tumorigenesis. However, whether any of the Rabs plays a metastasis suppressor role is least explored. Here we address the metastasis suppressive function of human Rab37 (hRAB37) using secretomics, cell, animal and clinical analyses. We show that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted glycoprotein that inhibits extracellular matrix turnover, is a novel cargo of hRAB37. hRAB37 regulates the exocytosis of TIMP1 in a nucleotide-dependent manner to inactivate matrix metalloproteinase 9 (MMP9) migration axis in vitro and in vivo. Dysfunction of hRAB37 or TIMP1 abrogates metastasis suppression. Lung cancer patients with metastasis and poor survival show low hRAB37 protein expression coinciding with low TIMP1 in tumours. Our findings identify hRAB37 as a novel metastasis suppressor Rab that functions through the TIMP1-MMP9 pathway and has significant prognostic power.

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“…It should also be noted that the findings of Pellinen et al [2006] and Caswell et al [2007] have fundamental differences. In the first place, the two Rabs appear to interact with different integrin subunits.…”

Section: Rabs Integrin Traffic and Cancer Cell Adhesion/migrationmentioning

confidence: 90%

“…Silencing of Rab25 resulted in exactly the opposite phenotypes. Caswell et al [2007] found that the b1 subunit of integrin and a5b1 heterodimers (but not avb3) could associate with over-expressed epitope-tagged Rab25 in A2780 ovarian cancer cells. This interaction was confirmed by reciprocal pull-down analysis, is GTP-dependent and is specific for Rab25, as neither Rab11A nor Rab11B interacted in the same manner.…”

Section: Rabs Integrin Traffic and Cancer Cell Adhesion/migrationmentioning

confidence: 92%

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Rabs and cancer cell motility

Tang

2009

Cell Motil. Cytoskeleton

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The Rab family of small GTPases functions in regulating vesicular transport in all eukaryotes. In the past few years, several important reports have linked some members of the Rab family to intriguing mechanistic aspects of cancer cell migration and invasiveness. Rab5 and Rab21 associate with a-integrin subunits and modulate their endosomal traffic and subcellular localization. Expression of the latter enhances adhesion and migration of certain cancer cell types. Rab25 has been functionally linked to tumor progression and the invasiveness of some epithelial cancers. Rab25 promotes invasive migration of cells in three-dimensional microenvironments by associating with a5b1 integrin, and directing its recycling to dynamic ruffling protrusions at the migrating cell front. Acting directly, or through its effector, the Rab-coupling protein, Rab25 could potentially engage both integrin and epidermal growth factor receptor and enhance their oncogenic recycling and signaling. Tumor invasiveness may also be modulated by Rab8-mediated exocytic traffic of MT1-matrix metalloproteinase, with the latter's activity likely influenced by interaction with the mammalian suppressor of Sec4 (Mss4), a Rab8 guanine nucleotide exchange factor, and integrin. We discuss highlights in the recent literature that point towards a role for Rab-mediated membrane traffic in cancer cell migration and invasion. Cell Motil.

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Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

Cited by 371 publications

References 41 publications

Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis

Rabs and cancer cell motility

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