Cytohesins/ARNO: the function in colorectal cancer cells

Tao Pan; Junfeng Sun; Jiyi Hu; Yiwang Hu; Jun Zhou; Zhigang Chen; Dong Xu; Wenhong Xu; Shu Zheng; Suzhan Zhang

doi:10.1371/journal.pone.0090997

Cytohesins/ARNO: the function in colorectal cancer cells

PLoS One. 2014 Mar 11;9(3):e90997. doi: 10.1371/journal.pone.0090997. eCollection 2014.

Authors

Tao Pan¹, Junfeng Sun², Jiyi Hu³, Yiwang Hu³, Jun Zhou³, Zhigang Chen³, Dong Xu⁴, Wenhong Xu⁴, Shu Zheng³, Suzhan Zhang³

Affiliations

¹ Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), Zhejiang University School of Medicine, Hangzhou, China.
² Department of Gastrointestinal Surgery, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China.
³ Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), Zhejiang University School of Medicine, Hangzhou, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / pathology
Disease Models, Animal
ErbB Receptors / metabolism
GTPase-Activating Proteins / antagonists & inhibitors
GTPase-Activating Proteins / genetics*
GTPase-Activating Proteins / metabolism*
Gene Expression
Gene Knockdown Techniques
Heterografts
Humans
Male
Mice
Receptor, IGF Type 1 / metabolism
Signal Transduction
Triazoles / administration & dosage
Triazoles / pharmacology
Tumor Burden / drug effects
Xenograft Model Antitumor Assays

Substances

GTPase-Activating Proteins
SecinH3
Triazoles
cytohesin-2
ErbB Receptors
Receptor, IGF Type 1

Grants and funding

This research was supported from National High Technology Research and Development Program of China (No. 2012AA02A506), Zhejiang Provincial Natural Science Foundation of China (LD13H160015) and Zhejiang Provincial Key Scientific and Technological Research Projects of International Cooperation (No. 2009C14010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.