Cancer Research Cancer Health Disparities Conference 2009  SU2C
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Cancer Research 68, 7561-7569, September 15, 2008. doi: 10.1158/0008-5472.CAN-08-0188
© 2008 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Lee, Y.-S.
Right arrow Articles by Yao, T.-P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, Y.-S.
Right arrow Articles by Yao, T.-P.

Molecular Biology, Pathobiology, and Genetics

The Cytoplasmic Deacetylase HDAC6 Is Required for Efficient Oncogenic Tumorigenesis

Yi-Shan Lee1, Kian-Huat Lim1, Xing Guo1, Yoshiharu Kawaguchi1, Yasheng Gao1, Tomasa Barrientos1, Peter Ordentlich2, Xiao-Fan Wang1, Christopher M. Counter1 and Tso-Pang Yao1,2

1 Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 2 Syndax Pharmaceuticals, Waltham, Massachusetts

Requests for reprints: Tso-Pang Yao, Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710. Phone: 919-613-8654; Fax. 919-668-3954; E-mail: yao00001{at}mc.duke.edu.

Key Words: HDAC6 • deacetylation • anoikis • transformation • HDACI

Histone deacetylase inhibitors (HDACI) are promising antitumor agents. Although transcriptional deregulation is thought to be the main mechanism underlying their therapeutic effects, the exact mechanism and targets by which HDACIs achieve their antitumor effects remain poorly understood. It is not known whether any of the HDAC members support robust tumor growth. In this report, we show that HDAC6, a cytoplasmic-localized and cytoskeleton-associated deacetylase, is required for efficient oncogenic transformation and tumor formation. We found that HDAC6 expression is induced upon oncogenic Ras transformation. Fibroblasts deficient in HDAC6 are more resistant to both oncogenic Ras and ErbB2-dependent transformation, indicating a critical role for HDAC6 in oncogene-induced transformation. Supporting this hypothesis, inactivation of HDAC6 in several cancer cell lines reduces anchorage-independent growth and the ability to form tumors in mice. The loss of anchorage-independent growth is associated with increased anoikis and defects in AKT and extracellular signal-regulated kinase activation upon loss of adhesion. Lastly, HDAC6-null mice are more resistant to chemical carcinogen-induced skin tumors. Our results provide the first experimental evidence that a specific HDAC member is required for efficient oncogenic transformation and indicate that HDAC6 is an important component underlying the antitumor effects of HDACIs. [Cancer Res 2008;68(18):7561–9]







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.