The role of the Rho GTPases in lens placode invagination

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

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Maturation of a postsynaptic domain: Role of small Rho GTPases in organising nicotinic acetylcholine receptor aggregates at the vertebrate neuromuscular junction

Journal of Anatomy ◽

10.1111/joa.13526 ◽

2021 ◽

Author(s):

Angelymar Medina‐Moreno ◽

Juan Pablo Henríquez

Keyword(s):

Neuromuscular Junction ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Rho Gtpases ◽

Nicotinic Acetylcholine ◽

Small Rho Gtpases

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TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19113428 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3428 ◽

Cited By ~ 14

Author(s):

Hyun-Jung Choi ◽

Na-Eun Kim ◽

Byeong Kim ◽

Miran Seo ◽

Ji Heo

Keyword(s):

Endothelial Cells ◽

Rho Gtpases ◽

Leukocyte Adhesion ◽

Hippo Pathway ◽

Specific Inhibitor ◽

Vascular Diseases ◽

Adhesive Properties ◽

Sprouting Angiogenesis ◽

Tnf Α

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

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Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Cells ◽

10.3390/cells9102167 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2167

Author(s):

Brock Humphries ◽

Zhishan Wang ◽

Chengfeng Yang

Keyword(s):

Breast Cancer ◽

Membrane Trafficking ◽

Rho Gtpases ◽

Migration And Invasion ◽

Breast Cancer Patients ◽

Cancer Initiation ◽

Cell Type Specific ◽

And Function ◽

Therapeutic Responses

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, tumor suppressor functions of Rho GTPases have also been revealed, suggesting a context and cell-type specific function for Rho GTPases in cancer. This review aims to summarize recent progresses in our understanding of the regulation and functions of Rho GTPases, specifically in the context of breast cancer. The potential of Rho GTPases as therapeutic targets and prognostic tools for breast cancer patients are also discussed.

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E-cadherin negatively regulates neoplastic growth in non-small cell lung cancer: role of Rho GTPases

Oncogene ◽

10.1038/onc.2010.39 ◽

2010 ◽

Vol 29 (19) ◽

pp. 2760-2771 ◽

Cited By ~ 40

Author(s):

L Asnaghi ◽

W C Vass ◽

R Quadri ◽

P M Day ◽

X Qian ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Rho Gtpases ◽

Small Cell ◽

Small Cell Lung ◽

Neoplastic Growth ◽

E Cadherin

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Dual Effects ofβ3Integrin Subunit Expression on Human Pancreatic Cancer Models

Analytical Cellular Pathology ◽

10.1155/2010/917013 ◽

2010 ◽

Vol 33 (5-6) ◽

pp. 191-205 ◽

Cited By ~ 1

Author(s):

S. Marchán ◽

S. Pérez-Torras ◽

A. Vidal ◽

J. Adan ◽

F. Mitjans ◽

...

Keyword(s):

Pancreatic Cancer ◽

Rho Gtpases ◽

Cell Attachment ◽

Human Pancreatic Cancer ◽

Cell Growth And Migration ◽

Subunit Expression ◽

And Migration

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.Methods: In view of these findings, we examined the role ofβ3in pancreatic cancer by generating two stableβ3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.Results: Transduction ofβ3selectively augmented the functional membraneαvβ3integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected inβ3-overexpressing cells. Moreover, tumors expressingβ3displayed reduced growth. Interestingly, treatment of mice with anαv-blocking antibody inhibited the growth ofβ3-expressing tumors to a higher extent.Conclusion: Our results collectively support the hypothesis thatαvβ3integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.

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