title: 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 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.
authors: Princess Margaret Cancer Center, University Health Network, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
authors: Daphna
authors: D
authors: Mokady
authors: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: dmeiri@technion.ac.il.
authors: David
authors: D
authors: Meiri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020741:rho GTP-Binding Proteins; D002945:Cisplatin
keywords: Cancer therapy; Chemoresistance; Cisplatin; Cytoskeleton; Drug resistance; RhoA; RhoGTPases; Rock