Loss of TACC1 variant25 inducing cell proliferation and suppressing autophagy in head and neck squamous carcinoma

Transforming acidic coiled-coil containing protein1 (TACC1) is closely related to transcription, translation and centrosome dynamics. Dysregulation of TACC1 is associated with multiple malignancies. Alternative splicing (AS) of TACC1 produces multiple variants, which are of great significance in cancer biology. However, the expression and biological functions of TACC1 variants in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we found for the first time that TACC1 variants exhibited a characteristic expression pattern and that TACC1 variant25 (TACC1v25) was downregulated in HNSCC tissues and cell lines. Overexpression of TACC1v25 in Cal27 and Fadu cells significantly inhibited proliferation and promoted autophagy. Moreover, expression levels of nuclear pERK and p-mTOR were significantly decreased, while the expression of Beclin-1 and the LC3II/LC3I ratio were increased in TACC1v25-overexpressed Cal27 and Fadu cells. After the addition of AKT activator SC79 to TACC1v25-overexpressed Cal27 and Fadu cells, the autophagy levels were remarkably rescued. In conclusion, TACC1v25 inhibits HNSCC progression through the ERK and AKT/mTOR pathways by inhibiting proliferation and increasing autophagy. TACC1v25 might have potential use as a tumour suppressor in HNSCC.

Automated summary

TACC1 variant 25 (TACC1v25) is downregulated in head and neck squamous cell carcinoma (HNSCC), inhibiting proliferation and promoting autophagy through the ERK and AKT/mTOR pathways, suggesting its potential as a tumor suppressor in HNSCC.