Wash functions downstream of Rho1 GTPase in a subset of<i>Drosophila</i>immune cell developmental migrations

Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

doi:10.1091/mbc.e14-08-1266

Cited by 24 publications

(49 citation statements)

References 59 publications

(90 reference statements)

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“…Wiskott-Aldrich syndrome protein and SCAR Homolog has previously been described as a scaffold to coordinate signals from Rho GTPase and actin nucleators for actin and microtubule cytoskeleton dynamics. (18) Malignant cells form aberrant actin-based protrusions such as invadopodia to initiate invasion and metastasis. (19) The hypothesis of CSC is attractive because it may explain treatment resistance and distant metastasis of cancer patients.…”

Section: Discussionmentioning

confidence: 99%

WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma

et al. 2017

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There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott‐Aldrich syndrome protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of the WASP family in cancer progression remains elusive. Here, we studied the role of WASP and SCAR Homolog (WASH), a recently identified WASP family member, in human esophageal squamous cell carcinoma (ESCC). Using three human ESCC cell lines, we found that WASH expression was significantly elevated in cancer stem‐like cells enriched by sphere formation assay. WASH knockdown decreased the sphere‐forming capacity of esophageal cancer cells whereas WASH over‐expression exhibited the opposite effect. Mechanistically, we identified interleukin‐8 (IL‐8) as a key downstream target of WASH. IL‐8 knockdown completely attenuated tumor sphere formation induced by WASH overexpression. WASH knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, high WASH levels were associated with poor clinical prognosis in a total of 145 human ESCC tissues. Collectively, our results suggest an essential role of the WASH/IL‐8 pathway in human ESCC by maintaining the stemness of cancer cells. Hence, targeting this pathway might represent a promising strategy to control human esophageal carcinoma.

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Section: Discussionmentioning

confidence: 99%

WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma

et al. 2017

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“…The role of WASH in developmental dispersal of immune cells during Drosophila embryogenesis is even unclear. RNAi-mediated knockdown of WASH partially affects the stereotypic migration of embryonic macrophages (Verboon et al, 2015), but the loss-of-function mutant macrophages are indistinguishable from wild type . By contrast, a more recent study demonstrates a conserved function in retromer-dependent endocytic recycling of the luminal protein Serpentine in Drosophila trachea development (Dong et al, 2013).…”

Section: Introductionmentioning

confidence: 96%

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Nagel

Bechtold

Rodríguez

et al. 2017

Journal of Cell Science

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The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH; also known as Washout in flies) is a conserved actin-nucleationpromoting factor controlling Arp2/3 complex activity in endosomal sorting and recycling. Previous studies have identified WASH as an essential regulator in Drosophila development. Here, we show that homozygous wash mutant flies are viable and fertile. We demonstrate that Drosophila WASH has conserved functions in integrin receptor recycling and lysosome neutralization. WASH generates actin patches on endosomes and lysosomes, thereby mediating both aforementioned functions. Consistently, loss of WASH function results in cell spreading and cell migration defects of macrophages, and an increased lysosomal acidification that affects efficient phagocytic and autophagic clearance. WASH physically interacts with the vacuolar (V)-ATPase subunit Vha55 that is crucial to establish and maintain lysosome acidification. As a consequence, starved flies that lack WASH function show a dramatic increase in acidic autolysosomes, causing a reduced lifespan. Thus, our data highlight a conserved role for WASH in the endocytic sorting and recycling of membrane proteins, such as integrins and the V-ATPase, that increase the likelihood of survival under nutrient deprivation.

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“…This perinuclear actin, as well as migration under confinement, is reduced by Arp2/3 inhibition or knock-down, but is not required for the confined movement of cells with low lamin levels and softer nuclei, suggesting that actin filaments facilitate migration through narrow spaces by promoting nuclear deformation [52]. In hemocytes, the Drosophila macrophage-like immune cells, depletion of Rho1, WASH, or Arp2/3 subunits reduces the formation of cellular protrusions and prevents a subset of migration events during development [53]; similar studies suggest that lamellipodia formation and migration of hemocytes in vivo require Scar/WAVE [54,55]. …”

Section: Introductionmentioning

confidence: 99%

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

Swaney

2016

Current Opinion in Cell Biology

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As the first de novo actin nucleator discovered, the Arp2/3 complex has been a central player in models of protrusive force production via the dynamic actin network. Here, we review recent studies on the functional role of the Arp2/3 complex in the migration of diverse cell types in different migratory environments. These findings have revealed an unexpected level of plasticity, both in how cells rely on the Arp2/3 complex for migration and other physiological functions and in the intricate modulation of the Arp2/3 complex by other actin regulators and upstream signaling cascades.

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Wash functions downstream of Rho1 GTPase in a subset ofDrosophilaimmune cell developmental migrations

Cited by 24 publications

References 59 publications

WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma

WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

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