RhoGTPases – A novel link between cytoskeleton organization and cisplatin resistance

Abstract For more than three decades, platinum compounds have been the first line treatment for a wide spectrum of solid tumors. Yet, cisplatin resistance is a major impediment in cancer therapy, and deciphering the mechanisms underlying chemoresistance is crucial for the development of novel therap...

Full description

Saved in:
Bibliographic Details
Published in:Drug resistance updates 2015-03, Vol.19, p.22-32
Main Authors: Mokady, Daphna, Meiri, David
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Cancer therapy
Chemoresistance
Cisplatin
Cisplatin - pharmacology
Cytoskeleton
Cytoskeleton - metabolism
Disease Progression
Drug Design
Drug resistance
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic - drug effects
Hematology, Oncology and Palliative Medicine
Humans
Infectious Disease
Neoplasms - drug therapy
Neoplasms - pathology
rho GTP-Binding Proteins - metabolism
RhoA
RhoGTPases
Rock
Up-Regulation - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract For more than three decades, platinum compounds have been the first line treatment for a wide spectrum of solid tumors. Yet, cisplatin resistance is a major impediment in cancer therapy, and deciphering the mechanisms underlying chemoresistance is crucial for the development of novel therapies with enhanced efficacy. The Rho subfamily of small GTPases plays a significant role in cancer progression, and a growing body of evidence points toward the involvement of these proteins in anticancer drug resistance, including cisplatin resistance. The cycling between active and inactive states, governed by the balance between their GEFs, GAPs and GDIs, RhoGTPases, acts as molecular switches with a pivotal role in actin cytoskeleton organization. The Rho subfamily of proteins is involved in many key cellular processes including adhesion, vesicular trafficking, proliferation, survival, cell morphology and cell–matrix interactions. Although RhoA, RhoB and RhoC are highly homologous and share some upstream regulators and downstream effectors, they each have different roles in cancer progression and chemoresistance. While RhoA and RhoC are upregulated in many tumors and can stimulate transformation, RhoB appears to exhibit tumor suppressor characteristics with proapoptotic effects. In the current review, we discuss the role of Rho subfamily of proteins in cancer, and focus on their involvement in intrinsic and acquired drug resistance.
ISSN:1368-7646
1532-2084
DOI:10.1016/j.drup.2015.01.001