Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs

Yohei Yamauchi; Yuki Miura; Yasunori Kanaho

doi:10.1016/j.jbior.2016.10.004

Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs

Adv Biol Regul. 2017 Jan:63:115-121. doi: 10.1016/j.jbior.2016.10.004. Epub 2016 Oct 18.

Authors

Yohei Yamauchi¹, Yuki Miura¹, Yasunori Kanaho²

Affiliations

¹ Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
² Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Electronic address: ykanaho@md.tsukuba.ac.jp.

PMID: 27776975
DOI: 10.1016/j.jbior.2016.10.004

Abstract

The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling.

Keywords: Anti-cancer drugs; Arf6; GAP; GEF; Invasion; Metastasis; Tumor angiogenesis; Tumor growth.

Publication types

Review

MeSH terms

ADP-Ribosylation Factor 6
ADP-Ribosylation Factors / antagonists & inhibitors
ADP-Ribosylation Factors / genetics*
ADP-Ribosylation Factors / metabolism
Adaptor Proteins, Signal Transducing / antagonists & inhibitors
Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Animals
Antineoplastic Agents / pharmacology
Cell Cycle Proteins / antagonists & inhibitors
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Chlorobenzenes
Disease Progression
Gene Expression Regulation, Neoplastic*
Guanine Nucleotide Exchange Factors / antagonists & inhibitors
Guanine Nucleotide Exchange Factors / genetics*
Guanine Nucleotide Exchange Factors / metabolism
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / metabolism
Neoplasms / pathology
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Purines / pharmacology
Pyrazoles / pharmacology
Pyrimidinones / pharmacology
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
Receptors, Cytoplasmic and Nuclear / genetics*
Receptors, Cytoplasmic and Nuclear / metabolism
Signal Transduction
Triazoles / pharmacology

Substances

ADP-Ribosylation Factor 6
Adaptor Proteins, Signal Transducing
Antineoplastic Agents
Cell Cycle Proteins
Chlorobenzenes
GIT1 protein, human
Guanine Nucleotide Exchange Factors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
IQSEC1 protein, human
NAV-2729
Nerve Tissue Proteins
PSD protein, human
Purines
Pyrazoles
Pyrimidinones
QS11 compound
Receptors, Cytoplasmic and Nuclear
SecinH3
Triazoles
phosphatidylinositol receptors
ADP-Ribosylation Factors
ARF6 protein, human