Downregulated expression of TSHR is associated with distant metastasis in thyroid cancer

Liu, Tianrun; Men, Qianqian; Su, Xuan; Chen, Weichao; Zou, Liping; Li, Qiuli; Song, Ming; Ouyang, Dian; Chen, Yanfeng; Li, Zhaoqu; Fu, Xin; Yang, Ankui

doi:10.3892/ol.2017.7122

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…Tg and Tshr expression levels were undetectable in all cell lines. Similar to thyroid transcription factors, loss of Tg and Tshr expression has been associated with disease progression [ 27 , 28 ]. Shweppe et al and Henderson et al similarly reported varying expression of thyroid-specific genes in their patient-derived thyroid cancer cell lines [ 14 , 15 ].…”

Section: Resultsmentioning

confidence: 99%

Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Caperton

Jolly

Massoll

et al. 2021

Cancers

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Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.

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Section: Resultsmentioning

confidence: 99%

Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Caperton

Jolly

Massoll

et al. 2021

Cancers

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“…EZH2‐induced silencing of Vash1 by promoter methylation has been implicated in the progression and metastasis of several cancers [Lu et al ]. Liu et al [] also reported that a lack of expression of Tshr was associated with distant metastasis and a poor survival rate. Mmp23 was downregulated in prostate cancer [Riddick et al ], while Lpar33 was downregulated in pancreatic malignancy.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide DNA methylation changes in transformed foci induced by nongenotoxic carcinogens

Hwang

Yeom

Eom

et al. 2019

Environ and Mol Mutagen

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In vitro cell transformation assays (CTA) have been proposed as a method to identify possible nongenotoxic carcinogens. However, the current protocols do not provide information on the mechanism of action of the test articles. In this study, we combined an in vitro Bhas 42 CTA and sequencing‐based DNA methylation profiling analysis to elucidate the carcinogenic mechanism associated with nongenotoxic carcinogens. Three nongenotoxic carcinogens were evaluated: cadmium chloride, methyl carbamate, and lithocholic acid. Methylation profiles were generated for the two nongenotoxic carcinogens (cadmium chloride and lithocholic acid) that were positive in Bhas 42 CTA. Methyl carbamate did not exhibit any promoter activity. Approximately 9.8% of all differentially methylated regions (DMRs) identified in cadmium chloride‐induced transformed foci overlapped with DMRs in lithocholic acid‐induced transformed foci. Interestingly, overlapping DMRs showed more hypermethylation than individual DMRs. In addition, the DMRs in CpG island elements common to both nongenotoxic carcinogens showed considerably more bias toward hypermethylated DMRs than those unique to either cadmium chloride or lithocholic acid. Pathway enrichment analysis revealed that genes harboring hypermethylated DMRs were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including pathways in cancer, basal cell carcinoma, and Wnt signaling. The genes harboring hypomethylated DMRs were significantly related to mRNA surveillance pathway, RNA transport, and autophagy. Taken together, our preliminary results on genome‐wide methylation analysis of cell clones from nongenotoxic carcinogen‐induced foci could be exploited for CTAs improvement, but further research will be required to standardize and assess the specificity and sensitivity of this combined approach. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

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“…Their results showed that a lack of TSHR contributes to the formation of distant metastasis in patients with differentiated thyroid cancers (DTC), which results in a poor survival rate. The expression of TSHR down-regulates cancer cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) of differentiated thyroid cancer cells [38].…”

Section: Prace Poglądowementioning

confidence: 99%

“…W badaniu wykazano, że brak TSHR sprzyja tworzeniu przerzutów u pacjentów ze zróżnicowanymi rakami tarczycy (DTC, differentiated thyroid cancer), co skutkuje gorszym rokowaniem. Natomiast ekspresja TSHR obniża inwazję komórek nowotworowych poprzez hamowanie przejścia nabłonkowo-mezenchymalnego (EMT, epithelial-mesenchymal transition) komórek DTC [38].…”

Section: Prace Poglądoweunclassified

Glycosylation of thyroid-stimulating hormone receptor

Korta

Pocheć

2019

Endokrynologia Polska

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Thyroid-stimulating hormone receptor (TSHR) is a typical membrane receptor with 7-transmembrane helix domain (7TMR), coupled to the G protein. The mature receptor, present in the cell membrane, is composed of the A subunit comprising a large extracellular domain, and the B subunit, which consists of a short extracellular fragment anchored in the cell membrane and an intracellular part. The TSH receptor is subject to numerous post-translational modifications that determine its final structure and significantly affect its activity. One of them is glycosylation. TSHR is abundantly N-glycosylated, due to the presence of six N-glycosylation sites in the extracellular domain (Asn77, Asn99, Asn113, Asn177, Asn198, Asn302), mostly evolutionarily conserved. N-glycans constitute 30-40% of the receptor molecular weight. The glycans are necessary for the receptor trafficking to the plasma membrane and binding of TSH to the receptor. Fucosylated and sialylated N-oligosaccharides were found on TSHR molecules. The increased sialylation of TSHR glycans correlates positively with the receptor binding ability and prolongs the time of receptor incorporation into the cell membrane. TSHR is the main autoantigen in Graves' disease (GD), one of the thyroid autoimmune diseases. One hypothesis assumes that the higher N-glycosylation of THSR in human compared to animals influences the breaking of autotolerance and GD development. N-oligosaccharides are the important part of THSR molecule, necessary for the proper functioning of receptors and probably involved in thyroid autoimmunity in GD.

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Downregulated expression of TSHR is associated with distant metastasis in thyroid cancer

Cited by 12 publications

References 28 publications

Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Genome‐wide DNA methylation changes in transformed foci induced by nongenotoxic carcinogens

Glycosylation of thyroid-stimulating hormone receptor

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