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Senescence Escape in Melanoma: Role of Spleen Tyrosine Kinase SYK

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Book cover Tumor Dormancy, Quiescence, and Senescence, Volume 2

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 2))

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Abstract

Tissue homeostasis is maintained by appropriate innate cellular responses to various oncogenic or genotoxic stresses. Flaws in pathways controlling these responses can cause cancer. Cellular senescence is a critical tumor suppressor mechanism and a well-recognized failsafe program against melanoma progression. Melanoma is a lethal skin cancer of increasing incidence that is linked to solar ultraviolet (UV) radiation and oncogenic events such as activating mutations in BRAF. Understanding why senescence fails to constraint malignant transformation of epidermal melanocytes is a key question in melanoma biology. Spleen tyrosine kinase (Syk) is a multifunction protein tyrosine kinase critical for immune and hematopoietic signaling that has been implicated in tumor suppression of several carcinomas and skin melanomas. Our recent report indicated that Syk exerts its melanoma suppressive function by inducing p53-dependent premature senescence and stress-activated c-Jun N-terminal kinases (JNKs) activation. We proposed that epigenetic inactivation of Syk that is generally observed in primary and metastatic melanoma cells may contribute to senescence escape and tumorigenicity. In this chapter, we discuss this new aspect of Syk function in melanomagenesis with a focus on cellular circuits controlling BRAFV600E-induced senescence. We also examine the potential implication of Syk in p53-mediated UVB stress signaling in melanocytes.

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Acknowledgements

This work was supported by INSERM and research grants from the ARC foundation.

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Authors and Affiliations

  1. C3M, Team Microenvironment, Signaling and Cancer, INSERM, U1065, Nice, France

    Marcel Deckert & Sophie Tartare-Deckert

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  1. Marcel Deckert
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  2. Sophie Tartare-Deckert
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Correspondence to Sophie Tartare-Deckert .

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Editors and Affiliations

  1. Department of Biological Sciences, Kean University, Room 213, Library Building, Union, New Jersey, USA

    M.A. Hayat

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Deckert, M., Tartare-Deckert, S. (2014). Senescence Escape in Melanoma: Role of Spleen Tyrosine Kinase SYK. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 2. Tumor Dormancy and Cellular Quiescence and Senescence, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7726-2_22

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