Docetaxel-Induced Cell Death Is Regulated by a Fatty Acid-Binding Protein 12-Slug-Survivin Pathway in Prostate Cancer Cells

Autor: Rong-Zong Liu, Mansi Garg, Xiao-Hong Yang, Roseline Godbout
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 25, Iss 17, p 9669 (2024)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms25179669
Popis: Chemotherapy is an important treatment option for advanced prostate cancer, especially for metastatic prostate cancer (PCa). Resistance to first-line chemotherapeutic drugs such as docetaxel often accompanies prostate cancer progression. Attempts to overcome resistance to docetaxel by combining docetaxel with other biological agents have been mostly unsuccessful. A better understanding of the mechanisms underlying docetaxel resistance may provide new avenues for the treatment of advanced PCa. We have previously found that the fatty acid-binding protein 12 (FABP12)-PPARγ pathway modulates lipid-related bioenergetics and PCa metastatic transformation through induction of Slug, a master driver of epithelial-to-mesenchymal transition (EMT). Here, we report that the FABP12-Slug axis also underlies chemoresistance in PCa cells. Cell sensitivity to docetaxel is markedly suppressed in FABP12-expressing cells, along with induction of Survivin, a typical apoptosis inhibitor, and inhibition of cleaved PARP, a hallmark of programmed cell death. Importantly, Slug depletion down-regulates Survivin and restores cell sensitivity to docetaxel in FABP12-expressing cells. Finally, we also show that high levels of Survivin are associated with poor prognosis in PCa patients, with FABP12 status determining its prognostic significance. Our research identifies a FABP12-Slug-Survivin pathway driving docetaxel resistance in PCa cells, suggesting that targeting FABP12 may be a precision approach to improve chemodrug efficacy and curb metastatic progression in PCa.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje