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Aberrant FGFR Tyrosine Kinase Signaling Enhances the Warburg Effect by Reprogramming LDH Isoform Expression and
Junchen Liu1,2, Guo Chen1,2, Zezhen Liu1,2
1Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China.
Cancer Research
|June 13, 2018
Summary
Fibroblast growth factor receptor 1 (FGFR1) reprograms prostate cancer cell metabolism. This reprogramming, by altering lactate dehydrogenase (LDH) isozymes, promotes tumor growth and is linked to poorer patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Ectopic fibroblast growth factor receptor 1 (FGFR1) expression is observed in prostate cancer progression, conferring growth and survival advantages.
- The precise mechanisms by which FGFR1 influences prostate cancer progression remain incompletely understood.
Purpose of the Study:
- To investigate how FGFR1 tyrosine kinase activity reprograms energy metabolism in prostate cancer cells.
- To elucidate the role of FGFR1 in regulating lactate dehydrogenase (LDH) isozymes and its impact on prostate cancer tumorigenicity.
Main Methods:
- Analysis of FGFR1's effect on lactate dehydrogenase A (LDHA) stability via tyrosine phosphorylation.
- Assessment of FGFR1's impact on lactate dehydrogenase B (LDHB) expression through promoter methylation.
- Evaluation of LDHA and LDHB depletion effects on prostate cancer cell tumorigenicity.
- Correlation of FGFR1 and LDH isozyme expression with patient survival and recurrence data.
Main Results:
- FGFR1 increases LDHA stability through tyrosine phosphorylation, promoting aerobic glycolysis.
- FGFR1 reduces LDHB expression via promoter methylation, further shifting metabolism towards glycolysis.
- Depletion of LDHA impaired tumor growth, while LDHB depletion enhanced it.
- Overexpression of FGFR1 and altered LDH isozyme expression correlated with shorter patient survival and increased biochemical recurrence.
Conclusions:
- FGFR1 signaling drives the Warburg effect in prostate cancer by differentially regulating LDHA and LDHB.
- Reprogramming of energy metabolism by FGFR1 is a key hallmark in prostate cancer progression.
- Aberrant FGFR1 and LDH isozyme expression serve as potential prognostic markers for prostate cancer patients.
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