期刊
MOLECULAR ONCOLOGY
卷 14, 期 12, 页码 3100-3120出版社
WILEY
DOI: 10.1002/1878-0261.12818
关键词
bioenergetics; epithelial-mesenchymal transition; fatty acid-binding proteins; metastasis; peroxisome proliferator-activated receptor gamma; prostate cancer
类别
资金
- Movember Discovery Grant from Prostate Cancer Canada [D2016-1307]
Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid-binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial-to-mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid beta-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPAR gamma activation which, in turn, regulates FABP12's role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP-PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.
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