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Targeting oncogenic β-catenin/CBP activity for the treatment of head and neck squamous cell carcinoma

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) presents primarily as oral squamous cell carcinoma (OSCC), an aggressive malignancy characterized by heterogeneity, locoregional metastases and resistance to existing treatments. Although a number of molecular alterations associated with OSCC have been identified, they have had limited impact on clinical management. A frequent feature of OSCC is the inappropriate activation of nuclear β-catenin. Here, we provide a comprehensive characterization of the effects of blocking the interaction between nuclear β-catenin and the cAMP-responsive element binding (CREB)-binding protein (CBP) using the small molecule inhibitor ICG-001. We demonstrate that ICG-001 inhibits cell proliferation and aggressive OSCC cell phenotypes in cellular, zebrafish and murine models, and that its inhibition-associated transcriptional signature tracks with advanced tumor grade and poor survival in human patients. Our results suggest that targeting the β-catenin/CBP interaction in the nucleus represents a new and effective therapy for OSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95704 | GEO | 2018/07/03

REPOSITORIES: GEO

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