Interaction between NF-κB and PLAC8 impairs autophagy providing a survival advantage to prostate cells transformed by cadmium

  • Sci Adv. 2025 Jun 13;11(24):eadv8640. doi: 10.1126/sciadv.adv8640.
Vaibhav Shukla  1 ,  Ashish Tyagi  1 ,  Balaji Chandrasekaran  1 ,  Bhawna Tyagi  1 ,  Balpreet Singh  1 ,  Thulasidharan Nair Devanarayanan  1 ,  Venkatesh Kolluru  2 ,  Murali K Ankem  2 ,  Chendil Damodaran  1
Affiliations
  • 1. College of Pharmacy, Texas A&M University, College Station, TX, USA.
  • 2. Department of Urology, University of Louisville, Louisville, KY, USA.
PMID: 40512859 DOI: 10.1126/sciadv.adv8640
Abstract

Prostate Cancer risk is influenced by various factors, including exposure to heavy metals like cadmium (Cd). The study reveals that the autophagy-regulating gene PLAC8 (placenta-specific 8) is significantly involved in Cd-induced prostate carcinogenesis, and NF-κB acts as the upstream transcriptional activator of PLAC8, which then selectively up-regulates Bcl-xL, providing a survival advantage to Cd-transformed cells. NF-κB activation stabilizes PLAC8 in the cytosol, disrupting Autophagy by allowing PLAC8 to colocalize with LC3B instead of LAMP1. Silencing NF-κB down-regulates PLAC8 and its survival function while inhibiting NF-κB or PLAC8, which restores Autophagy and decreases tumor growth in xenograft models. In addition, targeting Bcl-xL confirmed this signaling pathway. The findings suggest that sustained NF-κB activation regulates PLAC8 and highlights the NF-κB-PLAC8-BCL-xL axis as a potential target for early detection and therapies in metal-induced prostate Cancer.

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