2. Academic Validation
  3. CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer and Activator of Transcription 3

CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer and Activator of Transcription 3

  • J Invest Dermatol. 2022 Feb;142(2):425-434. doi: 10.1016/j.jid.2021.05.035.
Henri Montaudié 1,  Laura Sormani 2,  Bérengère Dadone-Montaudié 3,  Marjorie Heim 2,  Nathalie Cardot-Leccia 4,  Meri K Tulic 2,  Guillaume Beranger 2,  Anne-Sophie Gay 5,  Delphine Debayle 5,  Yann Cheli 6,  Jérémy H Raymond 7,  Pierre Sohier 7,  Valérie Petit 7,  Stéphane Rocchi 2,  Franck Gesbert 7,  Lionel Larue 7,  Thierry Passeron 8
Affiliations

Affiliations

  • 1 Team 12, Study of the melanocytic differentiation applied to vitiligo and melanoma: from the patient to the molecular mechanisms, Centre Méditerranéen de Médecine Moléculaire (C3M), Institut national de la santé et de la recherche médicale (INSERM) U1065, Université Nice Côte d'Azur, Nice, France; Department of Dermatology, Centre hospitalier universitaire (CHU) de Nice, Université Nice Côte d'Azur, Nice, France.
  • 2 Team 12, Study of the melanocytic differentiation applied to vitiligo and melanoma: from the patient to the molecular mechanisms, Centre Méditerranéen de Médecine Moléculaire (C3M), Institut national de la santé et de la recherche médicale (INSERM) U1065, Université Nice Côte d'Azur, Nice, France.
  • 3 Department of Pathology, Université Nice Côte d'Azur, Nice, France; Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284/ Institut national de la santé et de la recherche médicale (INSERM) U1081, CHU Nice, Université Nice Côte d'Azur, Nice, France.
  • 4 Department of Pathology, Université Nice Côte d'Azur, Nice, France.
  • 5 IPMC, CNRS, Université Côte d'Azur, Sophia Antipolis, France.
  • 6 Team 1, Biology and pathologies of melanocytes, Centre Méditerranéen de Médecine Moléculaire (C3M), Institut national de la santé et de la recherche médicale (INSERM) U1065, Université Nice Côte d'Azur, Nice, France.
  • 7 Normal and Pathological Development of Melanocytes, Institut Curie, Institut national de la santé et de la recherche médicale (INSERM) U1021, PSL Research University, Paris, France; UMR 3347, CNRS, Université Paris-Saclay, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • 8 Team 12, Study of the melanocytic differentiation applied to vitiligo and melanoma: from the patient to the molecular mechanisms, Centre Méditerranéen de Médecine Moléculaire (C3M), Institut national de la santé et de la recherche médicale (INSERM) U1065, Université Nice Côte d'Azur, Nice, France; Department of Dermatology, Centre hospitalier universitaire (CHU) de Nice, Université Nice Côte d'Azur, Nice, France. Electronic address: [email protected].
PMID: 34310951 DOI: 10.1016/j.jid.2021.05.035
Abstract

The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 Phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12B represses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.

Figures