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

Pan Xu,Jun Zhu,Chen-Yang Zhang,Yong Wang,Qian-Qian Zhang,Ran Zhao,Wei-Wen Jiang

doi:10.1038/s41420-021-00777-6

Abstract

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.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumours worldwide, accounting for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually [1]
Alternative splicing (AS) events are related to carcinogenesis; the importance of AS events in HNSCC has been emphasized at the genomic or transcriptional level [15, 26]
We focused on differential Transforming acidic coiled-coil containing protein1 (TACC1) variants in HNSCC

Summary

INTRODUCTION

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumours worldwide, accounting for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually [1]. As of December 2019, in GenBank, a total of 44 mRNA transcript variants have been described in human TACC1 (Gene ID:6867), including 31 encoding transcript variants, seven noncoding transcript variants and six predicted transcript variants. TACC1 and its variants are suggested to exhibit temporal and spatial expression patterns in human organs [15]. Full-length TACC1 positively regulates the Ras and mTOR pathways, and cooperates with them in colony formation, cell survival and tumorigenesis [18]. Ten TACC1 variants, inhibited proliferation and increased autophagy in HNSCC lines via including variants 3, 4, 8, 9, 11, 17, 20, 22, 23 and 30, were only the ERK and AKT/mTOR signalling pathways in HNSCC. Variants 2, 15, 26, 27, 28 and 31 were expressed in both NHOK and HNSCC cell lines (Fig. 1B). Variants 2, 26 and 27 were expressed in each cultured cells, variant 27

RESULTS

DISCUSSION

Findings

MATERIALS AND METHODS