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

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Science advances 📖 저널 OA 98.9% 2022: 1/1 OA 2023: 1/1 OA 2024: 4/4 OA 2025: 32/33 OA 2026: 49/49 OA 2022~2026 2025 Vol.11(24) p. eadv8640
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Shukla V, Tyagi A, Chandrasekaran B, Tyagi B, Singh B, Devanarayanan TN, Kolluru V, K Ankem M, Damodaran C

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Prostate cancer risk is influenced by various factors, including exposure to heavy metals like cadmium (Cd).

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APA Shukla V, Tyagi A, et al. (2025). Interaction between NF-κB and PLAC8 impairs autophagy providing a survival advantage to prostate cells transformed by cadmium.. Science advances, 11(24), eadv8640. https://doi.org/10.1126/sciadv.adv8640
MLA Shukla V, et al.. "Interaction between NF-κB and PLAC8 impairs autophagy providing a survival advantage to prostate cells transformed by cadmium.." Science advances, vol. 11, no. 24, 2025, pp. eadv8640.
PMID 40512859 ↗

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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