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AMPK and HIF signaling pathways regulate both longevity and cancer growth: the good news and the bad news about survival mechanisms

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Abstract

The AMP-activated protein kinase (AMPK) and hypoxia-inducible factor (HIF) signaling pathways are evolutionarily-conserved survival mechanisms responding to two fundamental stresses, energy deficiency and/or oxygen deprivation. The AMPK and HIF pathways regulate the function of a survival network with several transcription factors, e.g. FOXO, NF-κB, NRF2, and p53, as well as with protein kinases and other factors, such as mTOR, ULK1, HDAC5, and SIRT1. Given that AMPK and HIF activation can enhance not only healthspan and lifespan but also cancer growth in a context-dependent manner; it seems that cancer cells can hijack certain survival factors to maintain their growth in harsh conditions. AMPK activation improves energy metabolism, stimulates autophagy, and inhibits inflammation, whereas HIF-1α increases angiogenesis and helps cells to adapt to severe conditions. First we will review how AMPK and HIF signaling mechanisms control the function of an integrated survival network which is able not only to improve the regulation of longevity but also support the progression of tumorigenesis. We will also describe distinct crossroads between the regulation of longevity and cancer, e.g. specific regulation through the AMPKα and HIF-α isoforms, the Warburg effect, mitochondrial dynamics, and cellular senescence.

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Acknowledgments

This study was financially supported by the grants from the Academy of Finland, the University of Eastern Finland, VTR funding from Kuopio University Hospital, the Finnish Cultural Foundation, the Finnish Eye Foundation, and the Alfred Kordelin Foundation. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Antero Salminen

  2. Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Kai Kaarniranta

  3. Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029, KYS, Finland

    Kai Kaarniranta

  4. Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Anu Kauppinen

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  1. Antero Salminen
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Salminen, A., Kaarniranta, K. & Kauppinen, A. AMPK and HIF signaling pathways regulate both longevity and cancer growth: the good news and the bad news about survival mechanisms. Biogerontology 17, 655–680 (2016). https://doi.org/10.1007/s10522-016-9655-7

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