The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial-to-mesenchymal transition and lipid-derived energy production in prostate cancer cells.
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| Abstract |
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 β-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ 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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| Authors | Rong-Zong Liu, Won-Shik Choi, Saket Jain, Deepak Dinakaran, Xia Xu, Woo Hyun Han, Xiao-Hong Yang, Darryl D Glubrecht, Ronald B Moore, Hélène Lemieux, Roseline Godbout |
| Journal | Molecular oncology (Mol Oncol) Vol. 14 Issue 12 Pg. 3100-3120 (12 2020) ISSN: 1878-0261 [Electronic] United States |
| PMID | 33031638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. |
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