Dataset Information

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

ABSTRACT: 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 MYCN, YAP1, or TP53. Using retrospective cohort microarray data, we found that YAP1 is overexpressed in SHH alpha MB and patients profiled as resistant to SMO inhibitors compared to good responders. Here, we performed YAP1 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 SMO and YAP1 are enriched within cells of SHH MB. Importantly, our data suggest that YAP1 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.

SUBMITTER: Alencastro Veiga Cruzeiro G

PROVIDER: S-EPMC8699675 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Alencastro Veiga Cruzeiro Gustavo G de Almeida Magalhães Taciani T Ribeiro de Sousa Graziella G Bonfim Silva Ricardo R Alberto Oliveira de Biagi Junior Carlos C Ferreira das Chagas Pablo P Gomes de Paula Queiroz Rosane R Alberto Scrideli Carlos C Gonzaga Tone Luiz L Terci Valera Elvis E

Cancers 20211213 24

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 MYCN, YAP1, or TP53. Using retrospective cohort microarray data, we found that YAP1 is overexpressed in SHH alpha MB and patients profiled as resistant to SMO inhibitors compared ...[more]

PMID: 34944872

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Dataset Information

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

Publications

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

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