ΔNp63 regulates the expression of hyaluronic acid-related genes in breast cancer cells.

Triple negative breast cancers (TNBC) represent the most aggressive and clinically relevant breast carcinomas. On the basis of specific molecular signature, the majority of TNBC can be classified as basal-like breast carcinoma. Here, we report data showing that in basal-like breast carcinoma cells ΔNp63 is capable of sustaining the production of the hyaluronic acid (HA), one of the major component of the extracellular matrix (ECM).

ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and several molecular pathways that underlie the molecular tumorigenesis of HNSCC have been identified. Among them, amplification or overexpression of ΔNp63 isoforms is observed in the majority of HNSCCs. Here, we unveiled a ΔNp63-dependent transcriptional program able to regulate the metabolism and the signaling of hyaluronic acid (HA), the major component of the extracellular matrix (ECM).

Mathematical models of cancer metabolism.

Metabolism is essential for life, and its alteration is implicated in multiple human diseases. The transformation from a normal to a cancerous cell requires metabolic changes to fuel the high metabolic demands of cancer cells, including but not limited to cell proliferation and cell migration. In recent years, there have been a number of new discoveries connecting known aberrations in oncogenic and tumour suppressor pathways with metabolic alterations required to sustain cell proliferation and migration.

p63 regulates glutaminase 2 expression.

The transcription factor p63 is critical for many biological processes, including development and maintenance of epidermal tissues and tumorigenesis. Here, we report that the TAp63 isoforms regulate cell metabolism through the induction of the mitochondrial glutaminase 2 (GLS2) gene both in primary cells and tumor cell lines. By ChIP analysis and luciferase assay, we confirmed that TAp63 binds directly to the p53/p63 consensus DNA binding sequence within the GLS2 promoter region.