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

2020 ◽  
Vol 21 (3) ◽  
pp. 702
Author(s):  
Raffaela Mariarosaria Mariniello ◽  
Francesca Maria Orlandella ◽  
Anna Elisa De Stefano ◽  
Paola Lucia Chiara Iervolino ◽  
Giovanni Smaldone ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Biological Effects ◽  
Tumour Suppressor ◽  
Human Thyroid ◽  
Migration And Invasion ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cells

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.

scholarly journals Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines

2001 ◽  
Vol 169 (2) ◽  
pp. 417-424 ◽  
Author(s):  
M Iitaka ◽  
S Kakinuma ◽  
S Fujimaki ◽  
I Oosuga ◽  
T Fujita ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of thyroid cancer.

scholarly journals Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis

2011 ◽  
Vol 18 (5) ◽  
pp. 613-626 ◽  
Author(s):  
Kirk Jensen ◽  
Aneeta Patel ◽  
Joanna Klubo-Gwiezdzinska ◽  
Andrew Bauer ◽  
Vasyl Vasko
Keyword(s):  
Thyroid Cancer ◽  
Gap Junction ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Thyroid Cancer Cell ◽  
Gap Junctional ◽  
Thyroid Cancer Cells

Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell lines on poly-HEMA-treated low-adherent plates. We also performed immunohistochemical analysis of human cancer cells that had infiltrated blood and/or lymphatic vessels. Matrix deprivation was associated with establishment of contacts between floating thyroid cancer cells and formation of multi-cellular spheroids. This process was associated with activation of gap junctional transfer. Increased expression of the gap junction molecule Connexin43 was found in papillary and anaplastic cancer cells forming spheroids. All non-adherent cancer cells showed a lower proliferation rate compared with adherent cells but were more resistant to serum deprivation. AKT was constitutively activated in cancer cells forming spheroids. Inhibition of gap junctional transfer through Connexin43 silencing, or by treatment with the gap junction disruptor carbenoxolone, resulted in loss of pAKT and induction of apoptosis in a cell-type-specific manner. In human thyroid tissue, cancer cells that had infiltrated blood vessels showed morphological similarity to cancer cells forming spheroids in vitro. Intra-vascular cancer cells demonstrated prominent AKT activation in papillary and follicular cancers. Increased Connexin43 immunoreactivity was observed only in intra-vascular papillary cancer cells. Our data demonstrate that establishment of inter-cellular communication contributes to thyroid cancer cell resistance to anoikis. These findings suggest that disruption of gap junctional transfer could represent a potential therapeutic strategy for prevention of metastases.

scholarly journals Interplay between thyroid cancer cells and macrophages: effects on IL-32 mediated cell death and thyroid cancer cell migration

2019 ◽  
Vol 42 (5) ◽  
pp. 691-703 ◽  
Author(s):  
Yvette J. E. Sloot ◽  
Katrin Rabold ◽  
Thomas Ulas ◽  
Dennis M. De Graaf ◽  
Bas Heinhuis ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Migration ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Migration ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cells

scholarly journals FOXE1 regulates migration and invasion in thyroid cancer cells and targets ZEB1

2020 ◽  
Vol 27 (3) ◽  
pp. 137-151 ◽  
Author(s):  
Jesús Morillo-Bernal ◽  
Lara P Fernández ◽  
Pilar Santisteban
Keyword(s):  
Cell Migration ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Susceptibility ◽  
Human Thyroid ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Thyroid Cancer Cells

FOXE1 is a thyroid-specific transcription factor essential for thyroid gland development and maintenance of the differentiated state. Interestingly, a strong association has been recently described between FOXE1 expression and susceptibility to thyroid cancer, but little is known about the mechanisms underlying FOXE1-induced thyroid tumorigenesis. Here, we used a panel of human thyroid cancer-derived cell lines covering the spectrum of thyroid cancer phenotypes to examine FOXE1 expression and to test for correlations between FOXE1 expression, the allele frequency of two SNPs and a length polymorphism in or near the FOXE1 locus associated with cancer susceptibility, and the migration ability of thyroid cancer cell lines. Results showed that FOXE1 expression correlated with differentiation status according to histological sub-type, but not with SNP genotype or cell migration ability. However, loss-and-gain-of-function experiments revealed that FOXE1 modulates cell migration, suggesting a role in epithelial-to-mesenchymal transition (EMT). Our previous genome-wide expression analysis identified Zeb1, a major EMT inducer, as a putative Foxe1 target gene. Indeed, gene silencing of FOXE1 decreased ZEB1 expression, whereas its overexpression increased ZEB1 transcriptional activity. FOXE1 was found to directly interact with the ZEB1 promoter. Lastly, ZEB1 silencing decreased the ability of thyroid tumoral cells to migrate and invade, pointing to its importance in thyroid tumor mestastases. In conclusion, we have identified ZEB1 as a bona fide target of FOXE1 in thyroid cancer cells, which provides new insights into the role of FOXE1 in regulating cell migration and invasion in thyroid cancer.

scholarly journals Selumetinib Activity in Thyroid Cancer Cells: Modulation of Sodium Iodide Symporter and Associated miRNAs

2018 ◽  
Vol 19 (7) ◽  
pp. 2077 ◽  
Author(s):  
Sabine Wächter ◽  
Annette Wunderlich ◽  
Brandon Greene ◽  
Silvia Roth ◽  
Moritz Elxnat ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Sodium Iodide ◽  
Thyroid Cancer Cell ◽  
Sodium Iodide Symporter ◽  
Radioiodine Uptake ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Background: The MEK (mitogen-activated protein kinase)–inhibitor selumetinib led to increased radioiodine uptake and retention in a subgroup of patients suffering from radioiodine refractory differentiated thyroid cancer (RR-DTC). We aimed to analyse the effect of selumetinib on the expression of sodium iodide symporter (NIS; SLC5A5) and associated miRNAs in thyroid cancer cells. Methods: Cytotoxicity was assessed by viability assay in TPC1, BCPAP, C643 and 8505C thyroid cancer cell lines. NIS, hsa-let-7f-5p, hsa-miR-146b-5p, and hsa-miR-146b-3p expression was determined by quantitative RT-PCR. NIS protein was detected by Western blot. Radioiodine uptake was performed with a Gamma counter. Results: Selumetinib caused a significant reduction of cell viability in all thyroid cancer cell lines. NIS transcript was restored by selumetinib in all cell lines. Its protein level was found up-regulated in TPC1 and BCPAP cells and down-regulated in C643 and 8505C cells after treatment with selumetinib. Treatment with selumetinib caused a down-regulation of hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p in TPC1 and BCPAP cells. In 8505C cells, a stable or down-regulated hsa-miR-146b-5p was detected after 1h and 48h of treatment. C643 cells showed stable or up-regulated hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p. Selumetinib treatment caused an increase of radioiodine uptake, which was significant in TPC1 cells. Conclusions: The study shows for the first time that selumetinib restores NIS by the inhibition of its related targeting miRNAs. Further studies are needed to clarify the exact mechanism activated by hsa-miR-146b-5p, hsa-miR-146b-3p and hsa-let7f-5p to stabilise NIS. Restoration of NIS could represent a milestone for the treatment of advanced RR-DTC.

hMTH1 is required for maintaining migration and invasion potential of human thyroid cancer cells

DNA Repair ◽  
2018 ◽  
Vol 69 ◽  
pp. 53-62 ◽  
Author(s):  
Katarzyna D. Arczewska ◽  
Anna Stachurska ◽  
Maria Wojewódzka ◽  
Kamila Karpińska ◽  
Marcin Kruszewski ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Migration And Invasion ◽  
Invasion Potential ◽  
Thyroid Cancer Cells
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