Abstract
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.
Highlights
Tumour suppressor candidate 2 (TUSC2), known as FUS1, is located on the short arm of human chromosome 3 and behaves as a tumour suppressor in several human cancers [1]
We have previously showed that Tumor Suppressor Candidate 2 (TUSC2), a known tumour suppressor gene, is downregulated in human papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) compared to normal thyroid samples
We demonstrated that TUSC2 enhanced sensitivity to apoptotic treatment with doxorubicin (DOXO) or staurosporine (STS) and, through proteome profiler human apoptosis array and functional experiments, we unveiled that this effect was mediated in part by SMAC/DIABLO protein
Summary
Tumour suppressor candidate 2 (TUSC2), known as FUS1, is located on the short arm of human chromosome 3 and behaves as a tumour suppressor in several human cancers [1]. Loss or reduction of TUSC2 has been reported in non-small cell lung carcinomas (NSCLC), in small cell lung carcinomas [4], in mesothelioma [5], in oesophageal carcinoma [6], in glioblastoma [7] and in sarcomas [8]. These observations corroborate the significant impact of this tumour suppressor gene in human carcinogenesis. Deng and colleagues reported that forced expression of TUSC2 enhanced the antitumour activity of cisplatin in human lung cancer cells [9]; TUSC2 restoration sensitized lung cancer cells to treatment with EGFR inhibitors [10]. TUSC2 nanoparticles were administered intravenously, in clinical trials, in lung cancer patients [13] and showed safety and antitumour activity
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