Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells

Kazuo Kamemura; Akihiro Ito; Tadahiro Shimazu; Akihisa Matsuyama; Satoko Maeda; Tso-Pang Yao; Sueharu Horinouchi; Saadi Khochbin; Minoru Yoshida

doi:10.1016/j.bbrc.2008.06.092

Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells

Biochem Biophys Res Commun. 2008 Sep 12;374(1):84-9. doi: 10.1016/j.bbrc.2008.06.092. Epub 2008 Jul 3.

Authors

Kazuo Kamemura¹, Akihiro Ito, Tadahiro Shimazu, Akihisa Matsuyama, Satoko Maeda, Tso-Pang Yao, Sueharu Horinouchi, Saadi Khochbin, Minoru Yoshida

Affiliation

¹ Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.

PMID: 18602369
DOI: 10.1016/j.bbrc.2008.06.092

Abstract

Histone deacetylase 6 (HDAC6) is a multifunctional, cytosolic protein deacetylase that primarily acts on alpha-tubulin. Here we report that stable knockdown of HDAC6 expression causes a decrease in the steady-state level of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha, in A549 lung cancer cells. The decreased levels of in EGFR in HDAC6-knockdown cells, which correlated with increased acetylation of microtubules, were due to increased turnover of EGFR protein. Despite the decrease in EGFR levels, A549 cells lacking functional HDAC6 appeared to grow normally, probably due to increased expression of extracellular signal-regulated kinases 1 and 2. Indeed, HDAC6-knockdown cells were more sensitive than control cells to the MEK inhibitor U0126. These results suggest that HDAC6 inhibitors combined with inhibitors of growth factor signaling may be useful as cancer therapy.

Publication types

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

MeSH terms

Acetylation
Butadienes / pharmacology
Cell Line, Tumor
Cell Proliferation*
Down-Regulation
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / metabolism
Histone Deacetylase 6
Histone Deacetylase Inhibitors
Histone Deacetylases / genetics
Histone Deacetylases / physiology*
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / enzymology*
Lung Neoplasms / pathology
Microtubules / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Nitriles / pharmacology
Protein Kinase Inhibitors / pharmacology
Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
Receptor, Platelet-Derived Growth Factor alpha / metabolism

Substances

Butadienes
Histone Deacetylase Inhibitors
Nitriles
Protein Kinase Inhibitors
U 0126
ErbB Receptors
Receptor, Platelet-Derived Growth Factor alpha
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
HDAC6 protein, human
Histone Deacetylase 6
Histone Deacetylases