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dc.contributor.authorJu, J.A.
dc.contributor.authorGodet, I.
dc.contributor.authorDiGiacomo, J.W.
dc.date.accessioned2020-06-08T20:21:01Z
dc.date.available2020-06-08T20:21:01Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085533372&doi=10.1002%2fcnr2.1164&partnerID=40&md5=4f6e041e5d0a14e72e9deb9bf451eb2d
dc.identifier.urihttp://hdl.handle.net/10713/12991
dc.description.abstractBackground: RhoB is a Rho family GTPase that is highly homologous to RhoA and RhoC. RhoA and RhoC have been shown to promote tumor progression in many cancer types; however, a distinct role for RhoB in cancer has not been delineated. Additionally, several well-characterized studies have shown that small GTPases such as RhoA, Rac1, and Cdc42 are induced in vitro under hypoxia, but whether and how hypoxia regulates RhoB in breast cancer remains elusive. Aims: To determine whether and how hypoxia regulates RhoB expression and to understand the role of RhoB in breast cancer metastasis. Methods: We investigated the effects of hypoxia on the expression and activation of RhoB using real-time quantitative polymerase chain reaction and western blotting. We also examined the significance of both decreased and increased RhoB expression in breast cancer using CRISPR depletion of RhoB or a vector overexpressing RhoB in 3D in vitro migration models and in an in vivo mouse model. Results: We found that hypoxia significantly upregulated RhoB mRNA and protein expression resulting in increased levels of activated RhoB. Both loss of RhoB and gain of RhoB expression led to reduced migration in a 3D collagen matrix and invasion within a multicellular 3D spheroid. We showed that neither the reduction nor overexpression of RhoB affected tumor growth in vivo. While the loss of RhoB had no effect on metastasis, RhoB overexpression led to decreased metastasis to the lungs, liver, and lymph nodes of mice. Conclusion: Our results suggest that RhoB may have an important role in suppressing breast cancer metastasis.en_US
dc.description.sponsorshipWork is supported by National Institute of Health (National Cancer Institute, U54-CA210173 and R00-CA181352), V Scholar Foundation, Susan G. Komen Foundation (CCR17483484), the Jayne Koskinas Ted Giovanis Foundation for Health and Policy, and the Breast Cancer Research Foundation.en_US
dc.description.urihttp://doi.org/10.1002/cnr2.1164en_US
dc.language.isoen_USen_US
dc.publisherWiley-Blackwell Publishing Ltden_US
dc.relation.ispartofCancer Reports
dc.subjectbreast canceren_US
dc.subjectcancer metastasisen_US
dc.subjecthypoxiaen_US
dc.subjectRho GTPaseen_US
dc.subjectRhoBen_US
dc.titleRhoB is regulated by hypoxia and modulates metastasis in breast canceren_US
dc.typeArticleen_US
dc.identifier.doi10.1002/cnr2.1164


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