NKX3.1 Expression Contributes to Epithelial-Mesenchymal Transition of Prostate Cancer Cells

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Inflammation is linked to aggressive prostate cancer and metastasis, but mechanisms are unclear.
• Previous work showed conditioned media (CM) induces LNCaP cell migration, linked to NKX3.1 loss.
• This study investigates inflammation's role in prostate cancer cell migration and NKX3.1's function.

Purpose of the Study:

• To comprehensively analyze inflammation-mediated prostate cancer cell migration.
• To elucidate the role of the tumor suppressor NKX3.1 in this process.
• To understand the dynamic phenotypic changes, including epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET).

Main Methods:

• Utilized an optimized model of inflammation in the tumor microenvironment.
• Investigated time-dependent effects of CM exposure and NKX3.1 expression changes.
• Depleted NKX3.1 using CRISPR/Cas9 and analyzed migrating cells exposed to inflammatory cytokines.
• Performed quantitative proteomic analysis and KEGG pathway analysis.

Main Results:

• Inflammation-induced migration involves reversible loss of E-cadherin and altered vimentin expression, indicative of EMT.
• NKX3.1 depletion exacerbates migration and EMT phenotypes.
• Androgen receptor (AR)-mediated transcription contributes to MET during prostate cancer progression.
• Quantitative proteomics revealed subpopulations with distinct phenotypes, overexpressing proteins involved in metabolism and RNA processing; ABC transporters were significant.

Conclusions:

• Inflammation drives prostate cancer cell migration and heterogeneity through dynamic EMT/MET transitions.
• NKX3.1 plays a crucial role in regulating these migratory and phenotypic changes.
• Tumor microenvironment shifts influence cellular plasticity, impacting prostate cancer invasiveness and progression.