title: HDAC6 activity is not required for basal autophagic flux in metastatic prostate cancer cells.
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.
authors.affiliation: Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR 97331, USA Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Watson
authors.affiliation: Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Samanthi
authors.initials: S
authors.lastname: Wickramasekara
authors.affiliation: Genetics, Bioinformatics & Computational Biology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Maier
authors.affiliation: Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M Science Center, Houston, TX 77030, USA Department of Nutrition & Food Science, Texas A&M University, College Station, TX 77030, USA Department of Clinical Cancer Prevention, MD Anderson Cancer Center, Houston, TX 77030, USA Department of Molecular & Cellular Medicine, Texas A&M University College of Medicine, College Station, TX 77030, USA.
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Perez
authors.affiliation: Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA emily.ho@oregonstate.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
mesh_terms: D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D025941:Protein Interaction Mapping
chemical_list: C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: Autophagy; HDAC6; metastatic prostate cancer; tubacin