Ovarian Tumor Microenvironment Signaling: Convergence on the Rac1 GTPase

被引：28
作者：
Hudson, Laurie G. [1 ,2 ]
Gillette, Jennifer M. [2 ,3 ]
Kang, Huining [2 ,4 ]
Rivera, Melanie R. [2 ,3 ]
Wandinger-Ness, Angela [2 ,3 ]
机构：
[1] Univ New Mexico, Hlth Sci Ctr, Dept Pharmaceut Sci, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Hlth Sci Ctr, Ctr Comprehens Canc, Albuquerque, NM 87131 USA
[3] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[4] Univ New Mexico, Dept Med, Hlth Sci Ctr, Albuquerque, NM 87131 USA
来源：
CANCERS | 2018年 / 10卷 / 10期
基金：
美国国家卫生研究院;
关键词：
Rho-GTPase; Rac1; guanine nucleotide exchange factors (GEFs); GTPase activating proteins (GAPs); oncogene; oncoprotein; ovarian cancer; tumor microenvironment; bone niche; therapeutic targeting; EPITHELIAL-MESENCHYMAL TRANSITION; PLATINUM-BASED CHEMOTHERAPY; SMALL-MOLECULE INHIBITOR; RHO GTPASES; BREAST-CANCER; BONE-MARROW; SOMATIC MUTATIONS; SPLICE VARIANT; CELL-MIGRATION; C EXPRESSION;
D O I：
10.3390/cancers10100358
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：26
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