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

Overview of attention for article published in BMC Cancer, July 2017
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3 tweeters

Citations

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7 Dimensions

Readers on

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21 Mendeley
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Title
Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth
Published in
BMC Cancer, July 2017
DOI 10.1186/s12885-017-3470-7
Pubmed ID
Authors

Clarissa N. Amaya, Dianne C. Mitchell, Brad A. Bryan

Abstract

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. 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. 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. 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.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 24%
Researcher 4 19%
Student > Bachelor 4 19%
Student > Ph. D. Student 3 14%
Student > Doctoral Student 2 10%
Other 1 5%
Unknown 2 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 33%
Medicine and Dentistry 5 24%
Agricultural and Biological Sciences 3 14%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Immunology and Microbiology 1 5%
Other 2 10%
Unknown 2 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 April 2018.
All research outputs
#8,022,660
of 12,788,180 outputs
Outputs from BMC Cancer
#2,308
of 4,736 outputs
Outputs of similar age
#150,168
of 260,612 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 12,788,180 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,736 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
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