Cytosolic NUAK1 Enhances ATP Production by Maintaining Proper Glycolysis and Mitochondrial Function in Cancer Cells
| Autor: | Ariel F. Castro, Emilia Escalona, Roxana Pincheira, Alvaro A. Elorza, Marcelo Muñoz |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Bioenergetics oxidative cells seahorse assay cancer metabolism lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine mitochondrial donut medicine NUAK1 Glycolysis Original Research glycolytic switch Kinase Chemistry Cancer medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology Cytosol 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Cancer cell cell bioenergetic |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 10 (2020) |
| ISSN: | 2234-943X |
| Popis: | Indexación: Scopus. NUAK1 is an AMPK-related kinase located in the cytosol and the nucleus, whose expression associates with tumor malignancy and poor patient prognosis in several cancers. Accordingly, NUAK1 was associated with metastasis because it promotes cell migration and invasion in different cancer cells. Besides, NUAK1 supports cancer cell survival under metabolic stress and maintains ATP levels in hepatocarcinoma cells, suggesting a role in energy metabolism in cancer. However, the underlying mechanism for this metabolic function, as well as its link to NUAK1 subcellular localization, is unclear. We demonstrated that cytosolic NUAK1 increases ATP levels, which associates with increased mitochondrial respiration, supporting that cytosolic NUAK1 is involved in mitochondrial function regulation in cancer cells. NUAK1 inhibition led to the formation of “donut-like” structures, providing evidence of NUAK1-dependent mitochondrial morphology regulation. Additionally, our results indicated that cytosolic NUAK1 increases the glycolytic capacity of cancer cells under mitochondrial inhibition. Nuclear NUAK1 seems to be involved in the metabolic switch to glycolysis. Altogether, our results suggest that cytosolic NUAK1 participates in mitochondrial ATP production and the maintenance of proper glycolysis in cancer cells. Our current studies support the role of NUAK1 in bioenergetics, mitochondrial homeostasis, glycolysis and metabolic capacities. They suggest different metabolic outcomes depending on its subcellular localization. The identified roles of NUAK1 in cancer metabolism provide a potential mechanism relevant for tumor progression and its association with poor patient prognosis in several cancers. Further studies could shed light on the molecular mechanisms involved in the identified metabolic NUAK1 functions. © Copyright © 2020 Escalona, Muñoz, Pincheira, Elorza and Castro. https://www.frontiersin.org/articles/10.3389/fonc.2020.01123/full |
| Databáze: | OpenAIRE |
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