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Cancers 2018, 10(10), 358; https://doi.org/10.3390/cancers10100358

Ovarian Tumor Microenvironment Signaling: Convergence on the Rac1 GTPase

1
Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
2
Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
3
Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
4
Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Received: 1 September 2018 / Revised: 25 September 2018 / Accepted: 25 September 2018 / Published: 27 September 2018
(This article belongs to the Special Issue The Tumor Microenvironment of High Grade Serous Ovarian Cancer)
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Abstract

The tumor microenvironment for epithelial ovarian cancer is complex and rich in bioactive molecules that modulate cell-cell interactions and stimulate numerous signal transduction cascades. These signals ultimately modulate all aspects of tumor behavior including progression, metastasis and therapeutic response. Many of the signaling pathways converge on the small GTPase Ras-related C3 botulinum toxin substrate (Rac)1. In addition to regulating actin cytoskeleton remodeling necessary for tumor cell adhesion, migration and invasion, Rac1 through its downstream effectors, regulates cancer cell survival, tumor angiogenesis, phenotypic plasticity, quiescence, and resistance to therapeutics. In this review we discuss evidence for Rac1 activation within the ovarian tumor microenvironment, mechanisms of Rac1 dysregulation as they apply to ovarian cancer, and the potential benefits of targeting aberrant Rac1 activity in this disease. The potential for Rac1 contribution to extraperitoneal dissemination of ovarian cancer is addressed. View Full-Text
Keywords: Rho-GTPase; Rac1; guanine nucleotide exchange factors (GEFs); GTPase activating proteins (GAPs); oncogene; oncoprotein; ovarian cancer; tumor microenvironment; bone niche; therapeutic targeting Rho-GTPase; Rac1; guanine nucleotide exchange factors (GEFs); GTPase activating proteins (GAPs); oncogene; oncoprotein; ovarian cancer; tumor microenvironment; bone niche; therapeutic targeting
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Hudson, L.G.; Gillette, J.M.; Kang, H.; Rivera, M.R.; Wandinger-Ness, A. Ovarian Tumor Microenvironment Signaling: Convergence on the Rac1 GTPase. Cancers 2018, 10, 358.

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