Details

Autor(en) / Beteiligte

• Alencastro Veiga Cruzeiro, Gustavo
• de Almeida Magalhães, Taciani
• Ribeiro de Sousa, Graziella
• Bonfim Silva, Ricardo
• Alberto Oliveira de Biagi Junior, Carlos
• Ferreira das Chagas, Pablo
• Gomes de Paula Queiroz, Rosane
• Alberto Scrideli, Carlos
• Gonzaga Tone, Luiz
• Terci Valera, Elvis

Titel

YAP1 Is a Potential Predictive Molecular Biomarker for Response to SMO Inhibitor in Medulloblastoma Cells

Ist Teil von

• Cancers, 2021-12, Vol.13 (24), p.6249

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Advances in genomics have led to the identification of twelve relevant molecular subtypes within medulloblastoma (MB). The alpha subtype of Sonic hedgehog-driven MB is resistant to therapy (including smoothened inhibitors) due to activation of genes from the non-canonical SHH pathway, such as , , or . Using retrospective cohort microarray data, we found that is overexpressed in SHH alpha MB and patients profiled as resistant to SMO inhibitors compared to good responders. Here, we performed depletion via CRISPR/Cas9 in two in vitro models of SHH-like MB cells and found that this protein is involved in responsiveness to the SMO inhibitor regarding proliferation, apoptosis, and colony formation. Further, considering the synergic combination of YAP1 depletion with SMO inhibition, we assessed single-cell RNA-seq data from five patients and found that and are enriched within cells of SHH MB. Importantly, our data suggest that is not only a reliable biomarker for cellular response to SMOi but may indicate prospective testing of combination therapy using YAP1 and SMO inhibitors in preclinical models of SHH MB.