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| Status |
Public on Sep 04, 2023 |
| Title |
The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity was observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of PDHA1 Ser293 and LDHA Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.
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| Overall design |
The gene expression profiles of control HHUA endometrial cacer cells and BHLHE40-knockdown HHUA cells were examined using microarrays. Three replicates per group were analyzed.
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| Contributor(s) |
Asanoma K, Doi A |
| Citation(s) |
38301894 |
| Submission date |
Aug 30, 2023 |
| Last update date |
Feb 05, 2024 |
| Contact name |
Kazuo Asanoma |
| Organization name |
Kyushu University
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| Street address |
3-1-1 Maidashi, Higashi-ku
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| City |
Fukuoka City |
| State/province |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1010789 |
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