TitleHDAC6 activity is not required for basal autophagic flux in metastatic prostate cancer cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsWatson GW, Wickramasekara S, Fang Y, Maier CS, Williams DE, Dashwood RH, Perez VI, Ho E
JournalExp Biol Med (Maywood)
Volume241
Issue11
Pagination1177-85
Date Published2016 06
ISSN1535-3699
KeywordsAutophagy, Cell Line, Tumor, Cell Proliferation, Histone Deacetylase 6, Histone Deacetylases, Humans, Male, Protein Interaction Mapping
Abstract

Histone deacetylase 6 is a multifunctional lysine deacetylase that is recently emerging as a central facilitator of response to stress and may play an important role in cancer cell proliferation. The histone deacetylase 6-inhibitor tubacin has been shown to slow the growth of metastatic prostate cancer cells and sensitize cancer cells to chemotherapeutic agents. However, the proteins histone deacetylase 6 interacts with, and thus its role in cancer cells, remains poorly characterized. Histone deacetylase 6 deacetylase activity has recently been shown to be required for efficient basal autophagic flux. Autophagy is often dysregulated in cancer cells and may confer stress resistance and allow for cell maintenance and a high proliferation rate. Tubacin may therefore slow cancer cell proliferation by decreasing autophagic flux. We characterized the histone deacetylase 6-interacting proteins in LNCaP metastatic prostate cancer cells and found that histone deacetylase 6 interacts with proteins involved in several cellular processes, including autophagy. Based on our interaction screen, we assessed the impact of the histone deacetylase 6-inhibitor tubacin on autophagic flux in two metastatic prostate cancer cell lines and found that tubacin does not influence autophagic flux. Histone deacetylase 6 therefore influences cell proliferation through an autophagy-independent mechanism.

DOI10.1177/1535370215618518
Alternate JournalExp. Biol. Med. (Maywood)
PubMed ID26643866
PubMed Central IDPMC4950308
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States