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Updated: Sep 6, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
AMPK's double-faced role in advanced stages of prostate cancer
Faeze Gharibpoor1,2, Sara Kamali Zonouzi2,3, Sepideh Razi2,4,5
1Student Research Committee, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Abstract:
Prostate cancer (PCa) is the second leading cause of cancer deaths in men. Unfortunately, a very limited number of drugs are available for the relapsed and advanced stages of PCa, adding only a few months to survival; therefore, it is vital to develop new drugs. 5´ AMP-activated protein kinase (AMPK) is a master regulator of cell metabolism. It plays a significant role in the metabolism of PCa; hence, it can serve well as a treatment option for the advanced stages of PCa. However, whether this pathway contributes to cancer cell survival or death remains unknown. The present study reviews the possible pathways by which AMPK plays role in the advanced stages of PCa, drug resistance, and metastasis: (1) AMPK has a contradictory role in promoting glycolysis and the Warburg effect which are correlated with cancer stem cells (CSCs) survival and advanced PCa. It exerts its effect by interacting with hypoxia-induced factor 1 (HIF1) α, pyruvate kinase 2 (PKM2), glucose transporter (GLUT) 1 and pyruvate dehydrogenase complex (PDHC), which are key regulators of glycolysis; however, whether it promotes or discourage glycolysis is not conclusive. It can also exert an anti-CSC effect by negative regulation of NANOG and epithelial-mesenchymal transition (EMT) transcription factors, which are the major drivers of CSC maintenance; (2) the regulatory effect of AMPK on autophagy is also noticeable. Androgen receptors' expression increases AMPK activation through Calcium/calmodulin-dependent protein kinase 2 (CaMKK2) and induces autophagy. In addition, AMPK itself increases autophagy by downregulating the mammalian target of rapamycin complex (mTORC). However, whether increased autophagy inhibits or promotes cell death and drug resistance is contradictory. This study reveals that there are numerous pathways other than cell metabolism by which AMPK exerts its effects in the advanced stages of PCa, making it a priceless treatment target. Finally, we mention some drugs developed to treat the advanced stages of PCa by acting on AMPK.
Insights
5´ AMP-activated protein kinase (AMPK) plays a complex role in advanced prostate cancer (PCa) by influencing metabolism, cancer stem cells, and autophagy. Understanding these pathways is crucial for developing new PCa treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer (PCa) is a leading cause of cancer death in men, with limited treatment options for advanced stages.
- 5´ AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and a potential therapeutic target in PCa.
- The precise role of AMPK in PCa progression, including its impact on cancer stem cells (CSCs), drug resistance, and metastasis, remains unclear.
Purpose of the Study:
- To review the multifaceted roles of AMPK in advanced prostate cancer.
- To explore AMPK's involvement in glycolysis, the Warburg effect, and CSC survival.
- To investigate AMPK's regulatory effects on autophagy and its implications for cell death and drug resistance.
Main Methods:
- Literature review of studies investigating AMPK pathways in prostate cancer.
- Analysis of AMPK's interactions with key regulators of glycolysis (HIF1α, PKM2, GLUT1, PDHC).
- Examination of AMPK's influence on CSC markers (NANOG, EMT) and autophagy regulators (CaMKK2, mTORC).
Main Results:
- AMPK exhibits a contradictory role in glycolysis and the Warburg effect, potentially promoting CSC survival.
- AMPK can negatively regulate CSC maintenance factors like NANOG and EMT.
- AMPK modulates autophagy through androgen receptor signaling and mTORC, with unclear consequences for cell death and drug resistance.
Conclusions:
- AMPK has diverse roles in advanced PCa beyond metabolism, including effects on CSCs and autophagy.
- AMPK represents a promising therapeutic target for advanced prostate cancer.
- Further research is needed to elucidate the complex, context-dependent functions of AMPK in PCa progression and treatment.
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