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Senescence Escape in Melanoma: Role of Spleen Tyrosine Kinase SYK

  • Marcel Deckert
  • Sophie Tartare-Deckert
Chapter
Part of the Tumor Dormancy and Cellular Quiescence and Senescence book series (DOQU, volume 2)

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.

Keywords

c-Jun N-terminal kinases (JNK) activation Environmental stress Genetic disruption of p53 pathway Immunoreceptor tyrosine-based activation motifs (ITAMs) KIT, ERBB4 and CDK4 genes MDM2 activity and PTEN expression Melanocyte transformation Pathogenesis of melanoma Secreted protein acidic and rich in cysteine (SPARC) Syk in melanomagenesis 

Notes

Acknowledgements

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

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.C3M, Team Microenvironment, Signaling and CancerINSERM, U1065NiceFrance

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