The Role of Alcohol-Induced Golgi Fragmentation for Androgen Receptor Signaling in Prostate Cancer

Molecular Cancer Research : MCR
Sonia MancaArmen Petrosyan

Abstract

Multiple epidemiologic observations and meta-analysis clearly indicate the link between alcohol abuse and the incidence and progression of prostate cancer; however, the mechanism remains enigmatic. Recently, it was found that ethanol (EtOH) induces disorganization of the Golgi complex caused by impaired function of the largest Golgi matrix protein, giantin (GOLGB1), which, in turn, alters the Golgi docking of resident Golgi proteins. Here, it is determined that in normal prostate cells, histone deacetylase 6 (HDAC6), the known regulator of androgen receptor (AR) signaling, localizes in the cytoplasm and nucleus, while its kinase, glycogen synthase kinase β (GSK3β), primarily resides in the Golgi. Progression of prostate cancer is accompanied by Golgi scattering, translocation of GSK3β from the Golgi to the cytoplasm, and the cytoplasmic shift in HDAC6 localization. Alcohol dehydrogenase-generated metabolites induces Golgi disorganization in androgen-responsive LNCaP and 22Rv1 cells, facilitates tumor growth in a mouse xenograft model and activates anchorage-independent proliferation, migration, and cell adhesion. EtOH-treated cells demonstrate reduced giantin and subsequent cytoplasmic GSK3β; this phenomenon was validated in gi...Continue Reading

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Citations

Dec 19, 2019·Cells·Cole P FrisbieArmen Petrosyan
Nov 21, 2018·Biomolecules·Carol A CaseyArmen Petrosyan
Dec 25, 2019·Biochemistry. Biokhimii︠a︡·A Petrosyan
Dec 12, 2020·Journal of Cellular Physiology·Giovana Rampazzo TeixeiraFrancisco Eduardo Martinez

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