Dataset Information

RhoC Is an Unexpected Target of RhoGDI2 in Prevention of Lung Colonization of Bladder Cancer.

ABSTRACT: RhoGDI2 (ARHGDIB) suppresses metastasis in a variety of cancers but the mechanism is unclear, thus hampering development of human therapeutics. RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) for the Rho family of GTPases thought to primarily bind to Rac1; however, Rac1 activation was not decreased by RhoGDI2 expression in bladder cancer cells. To better understand the GTPase-binding partners for RhoGDI2, a mass spectrometry-based proteomic approach was used in bladder cancer cells. As expected, endogenous RhoGDI2 coimmunoprecipitates with Rac1 and unexpectedly also with RhoC. Further analysis demonstrated that RhoGDI2 negatively regulates RhoC, as knockdown of RhoGDI2 increased RhoC activation in response to serum stimulation. Conversely, overexpression of RhoGDI2 decreased RhoC activation. RhoC promoted bladder cancer cell growth and invasion, as knockdown increased cell doubling time, decreased invasion through Matrigel, and decreased colony formation in soft agar. Importantly, RhoC knockdown reduced in vivo lung colonization by bladder cancer cells following tail vein injection in immunocompromised mice. Finally, unbiased transcriptome analysis revealed a set of genes regulated by RhoGDI2 overexpression and RhoC knockdown in bladder cancer cells.RhoGDI2 suppresses bladder cancer metastatic colonization via negative regulation of RhoC activity, providing a rationale for the development of therapeutics that target RhoC signaling.

SUBMITTER: Griner EM

PROVIDER: S-EPMC4369172 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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RhoC Is an Unexpected Target of RhoGDI2 in Prevention of Lung Colonization of Bladder Cancer.

Griner Erin M EM Dancik Garrett M GM Costello James C JC Owens Charles C Guin Sunny S Edwards Michael G MG Brautigan David L DL Theodorescu Dan D

Molecular cancer research : MCR 20141216 3

<h4>Unlabelled</h4>RhoGDI2 (ARHGDIB) suppresses metastasis in a variety of cancers but the mechanism is unclear, thus hampering development of human therapeutics. RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) for the Rho family of GTPases thought to primarily bind to Rac1; however, Rac1 activation was not decreased by RhoGDI2 expression in bladder cancer cells. To better understand the GTPase-binding partners for RhoGDI2, a mass spectrometry-based proteomic approach was used in bl ...[more]

PMID: 25516960

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Project description:Background and objectiveA versatile biomarker, survivin, is highly expressed in proliferating cells of multiple cancers in humans and animals. It is an apoptosis-regulating protein, engaging in a cascade of reactions that involve several other genes and protein interactions. Currently, researchers are investigating its therapeutic potential due to the evidence linking its overexpression to advanced-stage lung cancer. This review is centered around examining survivin-related molecular mechanisms and its therapeutic role specifically in lung cancer. Our objective is to discuss the role of survivin in prognosis and treatment response, shedding light on immune-targeted therapies, as well as outlining future directions for survivin-based vaccines in lung cancer.MethodsThe PubMed database and the United States National Library of Medicine search engine at the National Institutes of Health were searched on 24 August 2023 to identify published research studies. Searching "((((((airway [Title/Abstract]) OR (lung [Title/Abstract])) OR (pulm[Title/Abstract])) OR (bronch[Title/Abstract])) OR (nslc[Title/Abstract])) AND (((cancer[Title/Abstract]) OR (carcino[Title/Abstract])) OR (oncol[Title/Abstract]))) AND (survivin[Title/Abstract])" gave 728 results. After screening the title and abstracts and excluding the review articles 168 titles were shortlisted and full text studied. The discussions are added to relevant sections.Key content and findingsSurvivin is a cell cycle-dependent, inhibitor of apoptosis protein that contributes to carcinogenesis, tumor vascularization, metastasis, and treatment resistance. Several treatments that impact survivin either directly or indirectly have been reported as effective in treating lung cancer. Immunity-based therapy, a novel approach known for its targeted nature and minimal side effects, is currently under investigation for lung cancer treatment. Emerging survivin-centered vaccines exhibit promising attributes in terms of safety, effectiveness, and ability to stimulate an immune response. These factors point towards a significant potential for advancing the future of lung cancer prevention and enhancing overall survival rates.ConclusionsNuclear survivin is a potential biomarker for advanced non-small cell lung cancer. It plays a role in determining drug responsiveness and is found to be significantly elevated in cases of resistance to chemotherapy. Multiple compounds and immunization strategies have been identified to impact lung cancer cells; however, they are currently in the early stages of phase I or phase II clinical trials. The substantial promise of survivin-based immunogenicity-focused treatments warrants in-depth investigation and exploration.

Dataset Information

RhoC Is an Unexpected Target of RhoGDI2 in Prevention of Lung Colonization of Bladder Cancer.

Publications

RhoC Is an Unexpected Target of RhoGDI2 in Prevention of Lung Colonization of Bladder Cancer.

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