English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background  The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells.    Methods  In this study, we compared ROCK1 and 2 protein expression in a large panel of benign and malignant vascular tumors to that of normal vasculature. We then utilized shRNA technology to knockdown the expression of ROCK1 and 2 in SVR tumor-forming vascular cells, and evaluated tumor size and proliferation rate in a xenograft model. Finally, we employed proteomics and metabolomics to assess how knockdown of the ROCK paralogs induced alterations in protein expression/phosphorylation and metabolite concentrations in the xenograft tumors.    Results  Our findings revealed that ROCK1 was overexpressed in malignant vascular tumors such as hemangioendotheliomas and angiosarcomas, and ROCK2 was overexpressed in both benign and malignant vascular tumors including hemangiomas, hemangioendotheliomas, hemangiopericytomas, and angiosarcomas. shRNA-mediated knockdown of ROCK2, but not ROCK1, in xenograft vascular tumors significantly reduced tumor size and proliferative index compared to control tumors. Proteomics and metabolomics analysis of the xenograft tumors revealed both overlapping as well as unique roles for the ROCK paralogs in regulating signal transduction and metabolite concentrations.    Conclusions  Collectively, these data indicate that ROCK proteins are overexpressed in diverse vascular tumors and suggest that specific targeting of ROCK2 proteins may show efficacy against malignant vascular tumors.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-017-3470-7) contains supplementary material, which is available to authorized users.

Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth