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Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1219))

Abstract

Hydrogen sulfide (H2S), while historically perceived merely as a toxicant, has progressively emerged as a key regulator of numerous processes in mammalian physiology, exerting its signaling function essentially through interaction with and/or modification of proteins, targeting mainly cysteine residues and metal centers. As a gaseous signaling molecule that freely diffuses across aqueous and hydrophobic biological milieu, it has been designated the third ‘gasotransmitter’ in mammalian physiology. H2S is synthesized and detoxified by specialized endogenous enzymes that operate under a tight regulation, ensuring homeostatic levels of this otherwise toxic molecule. Indeed, imbalances in H2S levels associated with dysfunctional H2S metabolism have been growingly correlated with various human pathologies, from cardiovascular and neurodegenerative diseases to cancer. Several cancer cell lines and specimens have been shown to naturally overexpress one or more of the H2S-synthesizing enzymes. The resulting increased H2S levels have been proposed to promote cancer development through the regulation of various cancer-related processes, which led to the interest in pharmacological targeting of H2S metabolism. Herein are summarized some of the key observations that place H2S metabolism and signaling pathways at the forefront of the cellular mechanisms that support the establishment and development of a tumor within its complex and challenging microenvironment. Special emphasis is given to the mechanisms whereby H2S helps shaping cancer cell bioenergetic metabolism and affords resistance and adaptive mechanisms to hypoxia.

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Acknowledgments

The Authors are grateful for funding from Ministero dell’Istruzione, dell’Università e della Ricerca of Italy (PNR-CNR Aging Program 2012–2014 and PRIN 20158EB2CM_003). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundação para a Ciência e Tecnologia/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged by CST and JBV.

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Authors and Affiliations

  1. CNR Institute of Molecular Biology and Pathology, Rome, Italy

    Alessandro Giuffrè & Karim Zuhra

  2. Instituto de Tecnologia Química e Biológica António Xavier, NOVA University of Lisbon, Oeiras, Portugal

    Catarina S. Tomé, Dalila G. F. Fernandes & João B. Vicente

  3. Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy

    Karim Zuhra

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  5. João B. Vicente
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Correspondence to Alessandro Giuffrè or João B. Vicente .

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  1. CEDOC, Chronic Diseases Research Centre, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal

    Jacinta Serpa

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Giuffrè, A., Tomé, C.S., Fernandes, D.G.F., Zuhra, K., Vicente, J.B. (2020). Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment. In: Serpa, J. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1219. Springer, Cham. https://doi.org/10.1007/978-3-030-34025-4_17

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