Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
J Pathol. 2009 Nov;219(3):347-55. doi: 10.1002/path.2604.
Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti-tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage-independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis.
人类肿瘤样盘(Tid1)是果蝇肿瘤抑制蛋白 Tid56 的人类同源物,参与多种细胞内信号通路,如细胞凋亡、细胞增殖和细胞存活。在这里,我们研究了 Tid1 在头颈部鳞状细胞癌(HNSCC)中的体外和体内抗肿瘤活性。首先,我们探讨了 Tid1 表达与 HNSCC 进展之间的临床相关性。通过对原发性 HNSCC 患者肿瘤组织的免疫组织化学分析发现,Tid1 的表达与肿瘤状态、复发和生存预后呈负相关。其次,在 HNSCC 细胞中异位表达 Tid1 显著抑制细胞增殖、迁移、侵袭、锚定非依赖性生长和异种移植肿瘤形成。第三,我们表明 Tid1 的过表达减弱了 EGFR 活性并阻断了 AKT 在 HNSCC 细胞中的激活,这已知参与了 HNSCC 细胞中存活的调节。另一方面,组成型激活 AKT 的异位表达大大降低了 Tid1 过表达诱导的细胞凋亡。综上所述,这些发现表明 Tid1 在 HNSCC 肿瘤发生中起肿瘤抑制作用。