The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein
The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein
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DOI：
10.3390/ijms21030702
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发表时间：
2020-02-01
影响因子：
5.6
通讯作者：
Salvatore, Giuliana
中科院分区：
文献类型：
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作者：
Mariniello, Raffaela Mariarosaria;Orlandella, Francesca Maria;Salvatore, Giuliana
甲状腺癌是最常见的内分泌癌，包括不同的形式。其中，甲状腺未分化癌（ATC）是最罕见但最致命的亚型，相比之下，甲状腺乳头状癌（PTC）显示出总体良好的预后。我们以前已经表明，肿瘤抑制因子候选2（TUSC 2），一个已知的肿瘤抑制基因，是下调人类PTC和ATC相比，正常甲状腺样本。本研究的目的是深入了解甲状腺癌细胞中TUSC 2诱导的分子机制。在这里，我们在乳头状（TPC-1）和间变性（8505 C）甲状腺癌细胞系中稳定转染了TUSC 2，并研究了其对几个生物学过程的影响，证明TUSC 2过表达降低了甲状腺癌细胞的增殖，迁移和侵袭。通过蛋白质组分析凋亡阵列，我们观察到TUSC 2通过增加SMAC/DIABLO和细胞色素C蛋白来增加对凋亡的敏感性。另一方面，在永生化甲状腺滤泡上皮细胞系（Nthy-ori 3-1）中，通过siRNA瞬时沉默TUSC 2显示出相反的效果。最后，SMAC/DIABLO的调节部分挽救了TUSC 2的生物学效应。因此，我们的数据突出了TUSC 2在甲状腺癌发生中的肿瘤抑制作用，表明它可能是甲状腺癌的一个有前途的靶点和生物标志物。
Thyroid carcinoma is the most common endocrine cancer and includes different forms. Among these, anaplastic thyroid carcinoma (ATC) is the rarest but the most lethal subtype, compared to papillary thyroid carcinoma (PTC) which shows an overall good prognosis. We have previously showed that Tumor Suppressor Candidate 2 (TUSC2), a known tumour suppressor gene, is downregulated in human PTC and ATC compared to normal thyroid samples. The aim of this study was to gain insight into the molecular mechanisms induced by TUSC2 in thyroid cancer cells. Here, we stably transfected TUSC2 in papillary (TPC-1) and in anaplastic (8505C) thyroid cancer cell lines and studied its effects on several biological processes, demonstrating that TUSC2 overexpression decreased thyroid cancer cell proliferation, migration and invasion. Through the proteome profiler apoptosis array, we observed that TUSC2 increased sensitivity to apoptosis by increasing the SMAC/DIABLO and CYTOCHROME C proteins. On the other hand, transient silencing of TUSC2, by siRNA, in an immortalized thyroid follicular epithelial cell line (Nthy-ori 3-1) showed the opposite effect. Finally modulation of SMAC/DIABLO partially rescued the biological effects of TUSC2. Thus, our data highlight a tumour suppressor role of TUSC2 in thyroid carcinogenesis, suggesting that it could be a promising target and biomarker for thyroid carcinoma.