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National Institute of Environmental Health Sciences

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Publication Detail

Title: Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis.

Authors: Kolluru, Venkatesh; Pal, Deeksha; Papu John, A M Sashi; Ankem, Murali K; Freedman, Jonathan H; Damodaran, Chendil

Published In Cancer Lett, (2017 11 01)

Abstract: Chronic exposure to cadmium is known to be a risk factor for human prostate cancer. Despite over-whelming evidence of cadmium causing carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal-induced cellular transformation remain unclear. Acute exposure (up to 72 h) to cadmium induces apoptosis in normal prostate epithelial cells (RWPE-1), while chronic exposure (>1 year) transforms these cells to a malignant phenotype (cadmium-transformed prostate epithelial cells; CTPE). Increased expression of autophagy-regulated genes; Plac8, LC3B and Lamp-1; in CTPE cells was associated with cadmium-induced transformation. Increased expression of Plac8, a regulator of autophagosome/autolysosome fusion, facilitates the pro-survival function of autophagy and upregulation of pAKT(ser473) and NF-κβ, to allow CTPE to proliferate. Likewise, inhibition of Plac8 suppresses CTPE cell growth. Additionally, overexpression of Plac8 in RWPE-1 cells induces resistance to cadmium toxicity. Pharmacological inhibitors and an inducer of autophagy failed to affect Plac8 expression and CTPE cell viability, suggesting a unique role for Plac8 in cadmium-induced prostate epithelial cell transformation. These results support a role for Plac8 as an essential component in the cadmium-induced transformation of normal prostate epithelial cells to a cancerous state.

PubMed ID: 28844710 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis/drug effects; Autophagy/drug effects*; Cadmium/toxicity*; Cell Proliferation/drug effects; Cell Transformation, Neoplastic/chemically induced; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology*; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Epithelial Cells/pathology; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Prostate/drug effects; Prostate/metabolism; Prostate/pathology*; Prostatic Neoplasms/chemically induced; Prostatic Neoplasms/genetics; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology*; Proteins/genetics; Proteins/metabolism*; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

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