Histone deacetylase inhibitors induce epithelial-to-mesenchymal transition in prostate cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Clinical use of histone deacetylase inhibitors (HDACIs) in solid tumors shows limited efficacy.
• The molecular mechanisms underlying HDACI treatment failure remain largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms behind treatment failure of HDACIs in prostate cancer (PCa).
• To explore the effects of HDACIs on cancer cell phenotypes and their implications for treatment strategies.

Main Methods:

• Treatment of PCa cells with HDACIs Trichostatin A (TSA) and Suberoylanilide hydroxamic acid (SAHA).
• Analysis of cellular morphology, gene expression (ZEB1, ZEB2, Slug, vimentin, N-cadherin, Fibronectin, Sox2, Nanog), and histone acetylation via CHIP assay.

Main Results:

• HDACIs induced an epithelial-to-mesenchymal transition (EMT) phenotype in PCa cells, characterized by increased mesenchymal markers.
• HDACIs also promoted cancer stem-like cell (CSLC) characteristics, including increased cell motility, and elevated Sox2 and Nanog expression.
• Histone 3 acetylation on gene promoters partially contributed to the increased expression of EMT markers.

Conclusions:

• HDACIs monotherapy may increase tumor aggressiveness by promoting EMT and CSLC phenotypes in prostate cancer.
• Reverting EMT to mesenchymal-to-epithelial transition (MET) or targeting CSLCs before HDACI treatment could enhance therapeutic efficacy for solid tumors, particularly PCa.