Regulating Rho GTPases and their regulators

Hodge, Richard G.; Ridley, Anne J.

doi:10.1038/nrm.2016.67

Cited by 734 publications

(714 citation statements)

References 175 publications

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“…Some protein kinases such as PKA, ROCK1, Src and Akt have been shown to phosphorylate RhoA, Rnd3 (RhoE), Cdc42 and Rac1, respectively. 20 In most cases, phosphorylation seems to have a negative effect on the activity of Rho GTPases. RhoA can be phosphorylated on serine 188 (Ser188) by PKA and this allows RhoGDIs to bind with higher affinity to RhoA, thereby increasing its translocation from membranes to the cytosol.…”

Section: Regulation Of Rho Gtpases By Post-translational Modificationsmentioning

confidence: 99%

“…20 In addition, a Rac1 splice variant Rac1b has enhanced intrinsic guanine nucleotide exchange, impaired GTPase activity and does not interact with RhoGDIs, leading to accumulation of the GTPbound conformation of Rac1b in cells.…”

Section: Regulation Of Typical Rho Gtpases By Gefs Gaps and Gdismentioning

confidence: 99%

“…Several Rho GTPases have been reported to undergo ubiquitination, including RhoA, Rac1, Rac1b, Cdc42, RhoB and RhoBTB2. 20,30,31 Ubiquitination has been proposed to be a mechanism to control the local activity of Rho GTPases 30,32,33 and it can affect either the GTP-bound form (active) or GDP-bound form (inactive), or both. For example, Rac1 is ubiquitinated only when in the active form and bound to the plasma membrane.…”

Section: Regulation Of Rho Gtpases By Post-translational Modificationsmentioning

confidence: 99%

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Rho GTPases: Regulation and roles in cancer cell biology

Haga

Ridley²

2016

Small GTPases

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417

390

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Rho GTPases are well known for their roles in regulating cell migration, and also contribute to a variety of other cellular responses. They are subdivided into 2 groups: typical and atypical. The typical Rho family members, including RhoA, Rac1 and Cdc42, cycle between an active GTP-bound and inactive GDP-bound conformation, and are regulated by GEFs, GAPs and GDIs, whereas atypical Rho family members have amino acid substitutions that alter their ability to interact with GTP/GDP and hence are regulated by different mechanisms. Both typical and atypical Rho GTPases contribute to cancer progression. In a few cancers, RhoA or Rac1 are mutated, but in most cancers expression levels and/or activity of Rho GTPases is altered. Rho GTPase signaling could therefore be therapeutically targeted in cancer treatment.

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Section: Regulation Of Rho Gtpases By Post-translational Modificationsmentioning

confidence: 99%

Section: Regulation Of Typical Rho Gtpases By Gefs Gaps and Gdismentioning

confidence: 99%

Section: Regulation Of Rho Gtpases By Post-translational Modificationsmentioning

confidence: 99%

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Rho GTPases: Regulation and roles in cancer cell biology

Haga

Ridley²

2016

Small GTPases

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417

390

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“…43 Rho GTPases regulate cytoskeletal rearrangement, essential for cell migration, invasion, and neuritogenesis, 43 and are relevant to neuroblastoma metastasis.…”

Section: Ndpk-a-relevant Molecular Determinants Of Neuroblastoma Metamentioning

confidence: 99%

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

Tan

␣Chang

2018

Laboratory Investigation

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NDPK-A, encoded by nm23-H1 (also known as NME1) was the first metastasis suppressor discovered. Much of the attention has been focused on the metastasis-suppressing role of NDPK-A in human tumors, including breast carcinoma and melanoma. However, compelling evidence points to a metastasis-promoting role of NDPK-A in certain tumors such as neuroblastoma and lymphoma. To balance attention on this contrariety of NDPK-A in different cancer types, this review addresses the metastasis-promoting role of NDPK-A in neuroblastoma. Neuroblastoma is an embryonic tumor, arising from neural crest cells that fail to differentiate into the sympathetic nervous system. We summarize and discuss nm23-H1 genetics and the prognosis of neuroblastoma, structural and functional changes associated with the S120G mutation of NDPK-A, as well as the evidence supporting the role of NDPK-A as a metastasis promoter. Also discussed are the NDPK-A relevant molecular determinants of neuroblastoma metastasis, and metastasis-relevant neural crest development. Because of NDPK-A's dichotomous role in tumor metastasis as both a suppressor and a promoter, tumor genome/exome profiles are necessary to identify the molecular drivers of metastasis in the NDPK-A network for developing tumor-specific therapies.

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“…Rho GTPases control many aspects of cell behavior ranging from the regulation of cytoskeletal organization, cell motility and cell polarity, to nuclear gene expression and control of cell growth (Hodge and Ridley, 2016). Rho proteins cycle between an active (GTP-bound) and an inactive (GDP-bound) state.…”

Section: Introductionmentioning

confidence: 99%

A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells

Goicoechea

Zinn

Awadia

et al. 2017

Journal of Cell Science

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One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. In summary, we have identified a novel signaling pathway involving SGEF, RhoG and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.

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Regulating Rho GTPases and their regulators

Cited by 734 publications

References 175 publications

Rho GTPases: Regulation and roles in cancer cell biology

Rho GTPases: Regulation and roles in cancer cell biology

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells

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