Xu Pan, Zhao Ran, Zhang Chen-Yang, Zhang Qian-Qian, Wang Yong, Zhu Jun, Jiang Wei-Wen
Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Cell Death Discov. 2021 Dec 11;7(1):386. doi: 10.1038/s41420-021-00777-6.
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.
含转化酸性卷曲螺旋蛋白1（TACC1）与转录、翻译及中心体动力学密切相关。TACC1的失调与多种恶性肿瘤有关。TACC1的可变剪接（AS）产生多种变体，这些变体在癌症生物学中具有重要意义。然而，TACC1变体在头颈部鳞状细胞癌（HNSCC）中的表达及生物学功能仍不清楚。在本研究中，我们首次发现TACC1变体呈现出特征性表达模式，且TACC1变体25（TACC1v25）在HNSCC组织和细胞系中表达下调。在Cal27和Fadu细胞中过表达TACC1v25可显著抑制增殖并促进自噬。此外，在过表达TACC1v25的Cal27和Fadu细胞中，核pERK和p-mTOR的表达水平显著降低，而Beclin-1的表达及LC3II/LC3I比值升高。在过表达TACC1v25的Cal27和Fadu细胞中添加AKT激活剂SC79后，自噬水平得到显著恢复。总之，TACC1v25通过抑制增殖和增加自噬，经由ERK和AKT/mTOR途径抑制HNSCC进展。TACC1v25可能在HNSCC中具有作为肿瘤抑制因子的潜在用途。
