HOXC6 overexpression stimulates cell migration and correlates with poor prognosis in head and neck squamous cell carcinoma

TL;DR

HOXC6 overexpression promotes cancer cell migration and is linked to worse outcomes in head and neck cancer, suggesting it could be a new target for treatment.

Contribution

This study identifies HOXC6 as a novel oncogenic driver and potential biomarker in head and neck squamous cell carcinoma.

Findings

HOXC6 overexpression correlates with malignant progression and poor survival in HNSCC.

Knockdown of HOXC6 reduces cell proliferation and migration in HNSCC cell lines.

HOXC6 is linked to immune evasion and dysregulation of cell cycle genes like E2F and G2M checkpoints.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and accounts for 2% of cancer-related deaths. Although the oncogenic role of HOXC6 in solid tumors is known, its functional relevance in HNSCC remains elusive. Using The Cancer Genome Atlas (TCGA, with 520 HNSCC samples) data and in vitro models, we investigated the functional role of HOXC6 in HNSCC. TCGA analysis revealed that HOXC6 overexpression in HNSCC tissues correlated with malignant progression and poor survival outcomes. In vitro studies confirmed HOXC6 overexpression in HNSCC cell lines, and knockdown of HOXC6 significantly reduced both cell proliferation and migration, highlighting the oncogenic role of HOXC6. Additionally, pathway analysis of RNA-seq data linked HOXC6 expression with immune evasion and dysregulation of cell cycle genes, particularly the E2F and G2M checkpoints. Furthermore, H3K27ac ChIP-seq data showed that histone acetylation at the HOXC6 promoter drives HOXC6 overexpression. This study identified HOXC6 as a key oncogenic driver in HNSCC and as a candidate biomarker for HNSCC. Targeting HOXC6 could pave the way for improved biomarker-driven approaches in HNSCC treatment to reduce recurrence and improve patient survival rates.

The online version contains supplementary material available at 10.1007/s00018-025-06039-3.

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