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EZH2-Mediated Primary Cilium Deconstruction Drives Metastatic Melanoma Formation

EZH2-Mediated Primary Cilium Deconstruction Drives Metastatic Melanoma Formation

Daniel Zingg, Julien Debbache, Rodrigo Peña-Hernández, Ana T Antunes, Simon M Schaefer, Phil F Cheng, Dario Zimmerli, Jessica Haeusel, Raquel R Calçada, Eylul Tuncer, Yudong Zhang, Raphaël Bossart, Kwok-Kin Wong, etc.

Cancer Cell. 2018 Jul 9;34(1):69-84.e14.

PMID: 30008323

Abstract:

Human melanomas frequently harbor amplifications of EZH2. However, the contribution of EZH2 to melanoma formation has remained elusive. Taking advantage of murine melanoma models, we show that EZH2 drives tumorigenesis from benign BrafV600E- or NrasQ61K-expressing melanocytes by silencing of genes relevant for the integrity of the primary cilium, a signaling organelle projecting from the surface of vertebrate cells. Consequently, gain of EZH2 promotes loss of primary cilia in benign melanocytic lesions. In contrast, blockade of EZH2 activity evokes ciliogenesis and cilia-dependent growth inhibition in malignant melanoma. Finally, we demonstrate that loss of cilia enhances pro-tumorigenic WNT/β-catenin signaling, and is itself sufficient to drive metastatic melanoma in benign cells. Thus, primary cilia deconstruction is a key process in EZH2-driven melanomagenesis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416105	EZH2 human			Price

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