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An RNAi screen of Rho signalling networks identifies RhoH as a regulator of Rac1 in prostate cancer cell migration

Overview of attention for article published in BMC Biology, March 2018
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Title
An RNAi screen of Rho signalling networks identifies RhoH as a regulator of Rac1 in prostate cancer cell migration
Published in
BMC Biology, March 2018
DOI 10.1186/s12915-018-0489-4
Pubmed ID
Authors

Virginia Tajadura-Ortega, Ritu Garg, Richard Allen, Claudia Owczarek, Michael D. Bright, Samuel Kean, Aisyah Mohd-Noor, Anita Grigoriadis, Timothy C. Elston, Klaus M. Hahn, Anne J. Ridley

Abstract

Cell migration is essential for development and tissue repair, but it also contributes to disease. Rho GTPases regulate cell migration, but a comprehensive analysis of how each Rho signalling component affects migration has not been carried out. Through an RNA interference screen, and using a prostate cancer cell line, we find that approximately 25% of Rho network components alter migration. Some genes enhance migration while others decrease basal and/or hepatocyte growth factor-stimulated migration. Surprisingly, we identify RhoH as a screen hit. RhoH expression is normally restricted to haematopoietic cells, but we find it is expressed in multiple epithelial cancer cell lines. High RhoH expression in samples from prostate cancer patients correlates with earlier relapse. RhoH depletion reduces cell speed and persistence and decreases migratory polarity. Rac1 activity normally localizes to the front of migrating cells at areas of dynamic membrane movement, but in RhoH-depleted cells active Rac1 is localised around the whole cell periphery and associated with membrane regions that are not extending or retracting. RhoH interacts with Rac1 and with several p21-activated kinases (PAKs), which are Rac effectors. Similar to RhoH depletion, PAK2 depletion increases cell spread area and reduces cell migration. In addition, RhoH depletion reduces lamellipodium extension induced by PAK2 overexpression. We describe a novel role for RhoH in prostate cancer cell migration. We propose that RhoH promotes cell migration by coupling Rac1 activity and PAK2 to membrane protrusion. Our results also suggest that RhoH expression levels correlate with prostate cancer progression.

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Geographical breakdown

Country Count As %
Unknown 40 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 25%
Student > Bachelor 6 15%
Researcher 6 15%
Student > Ph. D. Student 5 13%
Student > Postgraduate 2 5%
Other 4 10%
Unknown 7 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 45%
Agricultural and Biological Sciences 5 13%
Nursing and Health Professions 2 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Unspecified 1 3%
Other 4 10%
Unknown 9 23%