PT  - JOURNAL ARTICLE
AU  - Punzi Simona
AU  - Balestrieri Chiara
AU  - D’Alesio Carolina
AU  - Bossi Daniela
AU  - Dellino Gaetano Ivan
AU  - Gatti Elena
AU  - Pruneri Giancarlo
AU  - Criscitiello Carmen
AU  - Carugo Alessandro
AU  - Curigliano Giuseppe
AU  - Natoli Gioacchino
AU  - Pelicci Pier Giuseppe
AU  - Lanfrancone Luisa
TI  - WDR5 regulates epithelial-to-mesenchymal transition in breast cancer cells <em>via</em> TGFβ
AID  - 10.1101/348532
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 348532
4099  - http://biorxiv.org/content/early/2018/06/16/348532.short
4100  - http://biorxiv.org/content/early/2018/06/16/348532.full
AB  - Even if the mortality rate in breast cancer (BC) has recently decreased, development of metastases and drug resistance are still challenges to successful systemic treatment. The epithelial-to-mesenchymal transition (EMT), as well as epigenetic dynamic modifications, plays a pivotal role in invasion, metastasis, and drug resistance. Here, we report that WDR5, the core subunit of histone H3 K4 methyltransferase complexes, is crucial in coordinating EMT and regulating epigenetic changes that drive metastasis. We show that silencing of WDR5 in BC up-regulates an epithelial signature in triple negative and luminal B like patients by transcriptional repression of mesenchymal genes and reduction of the metastatic properties of these cells. Moreover, we demonstrate that this regulation is mediated by inhibition of the TGFβ signaling both at the transcriptional and post-translational level, suggesting an active role of WDR5 in guiding tumor plasticity upon oncogenic insults, regardless of the pathological BC subtypes.We therefore suggest that WDR5 inhibition could be a successful pharmacologic approach to inhibit EMT and sensitize breast cancer cells to chemotherapy.