Cytohesins/ARNO: the function in colorectal cancer cells

• Published in: PloS one Vol. 9; no. 3; p. e90997
• Main Authors: Pan, Tao, Sun, Junfeng, Hu, Jiyi, Hu, Yiwang, Zhou, Jun, Chen, Zhigang, Xu, Dong, Xu, Wenhong, Zheng, Shu, Zhang, Suzhan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.03.2014; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Cancer; Cell differentiation; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell survival; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Disease Models, Animal; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; Gastrointestinal diseases; Gene Expression; Gene Knockdown Techniques; GTPase-Activating Proteins - antagonists & inhibitors; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Heterografts; Humans; Insulin; Insulin-like growth factor I; Male; Medicine; Mice; Receptor, Epidermal Growth Factor - metabolism; Receptor, IGF Type 1 - metabolism; Regulators; Signal Transduction; siRNA; Triazoles - administration & dosage; Triazoles - pharmacology; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090997

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) are critical regulators of cell differentiation, survival, proliferation, and migration in cancers. This study found that ARNO (cytohesin-2), an activator of the EGF and IGF-I pathways, was more highly expressed in colorectal cancer tissue than in benign adjacent colorectal tissue. When ARNO-siRNA or the chemical inhibitor SecinH3 blocked ARNO, the downstream of the EGF and IGF-I pathways decreased in colorectal cell lines HT29 and HCT116. This blocking also weakened cell proliferation, invasion, and migration in vitro. Furthermore, EGF receptor (EGFR)-dependent colorectal tumor xenografts in nude mouse exerted anti-proliferative and growth suppression effects by injecting secineH3. These data suggested that inhibiting cytohesins or ARNO as cytoplasmic activators of EGFR and IGF-I in colorectal cancer resulted in anti-proliferation, reduced invasion, decreased migration, and suppressed growth in vivo and in vitro. Therefore, cytohesins or ARNO may be a potential therapy target for some colorectal cancer.