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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| Authors: | Rong&#x;Zong Liu Won&#x;Shik Choi Saket Jain Deepak Dinakaran Xia Xu Woo Hyun Han Xiao&#x;Hong Yang Darryl D Glubrecht Ronald B Moore Hlne Lemieux Roseline Godbout |
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| Institution: | 1. Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton AB, Canada ; 2. Faculty Saint‐Jean, University of Alberta, Edmonton AB, Canada ; 3. Department of Surgery, University of Alberta, Edmonton AB, Canada |
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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.Abbreviations- AR
- androgen receptor
- ATP
- adenosine triphosphate
- CN
- copy number
- CPT1
- carnitine palmitoyltransferase I
- CS
- citrate synthase
- EMT
- epithelial–mesenchymal transition
- ET
- electron transfer‐state
- FABP
- fatty acid‐binding protein
- LD
- lipid droplet
- OA
- oleic acid
- PCa
- prostate cancer
- PPAR
- peroxisome proliferator‐activated receptor
- PPRE
- peroxisome proliferator‐activated receptor response element
- TZD
- thiazolidinediones
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| Keywords: | bioenergetics epithelial– mesenchymal transition fatty acid‐ binding proteins metastasis peroxisome proliferator‐ activated receptor gamma prostate cancer |
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