The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein

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.

Identification and Characterization of Long Non-coding RNAs in the Intestine of Olive Flounder (Paralichthys olivaceus) During Edwardsiella tarda Infection

“…Besides, dad1 is required for proper processing of N-linked glycoproteins and for certain cell survival in the mouse ( 44 ), and functional loss of dad1 in Drosophila would lead to a reduction of tissue growth due to increased apoptosis and lack of cell proliferation ( 45 ). The tusc2, a known tumor suppressor gene, is downregulated in non-small cell lung carcinomas, small cell lung carcinomas, mesothelioma, esophageal carcinoma, thyroid carcinoma, glioblastoma and sarcomas ( 46 ). The TUSC2 protein plays an important role in regulating a wide range of cellular processes, such as cell cycle arrest and apoptosis, in modulating the function of several kinases and affecting gene expression ( 47 , 48 ).…”

Cell and Molecular Biology of Thyroid Disorders 2.0

“…In this Special Issue, a total of 12 excellent papers consisting of eight original articles [ 6 , 7 , 10 , 22 , 23 , 24 , 25 , 26 ], and four reviews [ 19 , 27 , 28 , 29 ] were published, as detailed in Table 1 .…”

“…This collection includes nine manuscripts focusing on TC [ 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], two research articles on the topic of Graves’ disease [ 6 , 7 ], and one article with focus on central congenital hypothyroidism [ 10 ]. The TC studies published in this issue focused on prognostic, predictive markers or biomarkers [ 23 , 24 , 25 , 27 ], oncogenes [ 22 ] of TC, and anti-cancer drugs [ 19 , 26 , 28 , 29 ].…”

“…PTC are diagnosed very often and have a very good prognosis, whereas ATC are rare and have a worse prognosis [ 11 , 12 , 24 ]. Tumour Suppressor Candidate 2 ( TUSC2 ) is downregulated in ATC and PTC compared to benign thyroid tissue.…”

“…Tumour Suppressor Candidate 2 ( TUSC2 ) is downregulated in ATC and PTC compared to benign thyroid tissue. Mariniello et al [ 24 ] showed in vitro that TUSC2 overexpression reduced proliferation, migration, and the invasive potential of TC cells. In addition, TUSC2 elevated the TC cells’ sensitivity to apoptosis by induction of SMAC/DIABLO and cytochrome C proteins [ 24 ].…”