scholarly journals p53 family proteins in thyroid cancer

2007 ◽  
Vol 14 (1) ◽  
pp. 43-60 ◽  
Author(s):  
R Malaguarnera ◽  
V Vella ◽  
R Vigneri ◽  
F Frasca
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Protein Function ◽  
Cancer Biology ◽  
Diagnostic Procedures ◽  
Dominant Negative ◽  
P53 Family ◽  
Aberrant Expression ◽  
Poorly Differentiated ◽  
High Degree

At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial. Regulation of p53 family protein function depends on: (1) the balance between the expression of transcriptionally active (p53, TAp63, and TAp73) and inactive isoforms (ΔNp63 and ΔNp73); (2) their interaction and competition at DNA-responsive elements; (3) their interaction with regulatory proteins, either inhibitory or activating. In thyroid cancer, therefore, although mutations of the p53 oncosuppressor protein family are rare, other mechanisms are present, including aberrant expression of p53 family dominant negative isoforms, up-regulation of inhibitory proteins, and functional inhibition of activating proteins. The overall result is a defective oncosuppressor activity. These inactivating mechanisms may be present in the early stages of thyroid cancer and in different cancer histotypes. A better understanding of this complex network may not only ameliorate our comprehension of cancer biology, but also open the possibility of innovative diagnostic procedures and the development of targeted therapies.

scholarly journals Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma

Thyroid ◽  
2019 ◽  
Vol 29 (10) ◽  
pp. 1425-1437
Author(s):  
Alyaksandr V. Nikitski ◽  
Susan L. Rominski ◽  
Vincenzo Condello ◽  
Cihan Kaya ◽  
Mamta Wankhede ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Cancer Progression ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated

scholarly journals Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 367 ◽  
Author(s):  
Melnik ◽  
Sahana ◽  
Corydon ◽  
Kopp ◽  
Nassef ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Signal Pathways ◽  
Dependent Manner ◽  
Spheroid Formation ◽  
Mesenchymal Transition

Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.

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

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1094
Author(s):  
Caitlin O. Caperton ◽  
Lee Ann Jolly ◽  
Nicole Massoll ◽  
Andrew J. Bauer ◽  
Aime T. Franco
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
In Vitro Models ◽  
Follicular Thyroid Cancer ◽  
Poorly Differentiated

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.

scholarly journals MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Cesar Seigi Fuziwara ◽  
Edna Teruko Kimura
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Cell Biology ◽  
Cancer Biology ◽  
Anaplastic Thyroid Cancer ◽  
Genetic Alterations ◽  
Thyroid Tumor ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Approach

Anaplastic thyroid cancer (ATC) is among the most lethal types of cancers, characterized as a fast-growing and highly invasive thyroid tumor that is unresponsive to surgery and radioiodine, blunting therapeutic efficacy. Classically, genetic alterations in tumor suppressorTP53are frequent, and cumulative alterations in different signaling pathways, such as MAPK and PI3K, are detected in ATC. Recently, deregulation in microRNAs (miRNAs), a class of small endogenous RNAs that regulate protein expression, has been implicated in tumorigenesis and cancer progression. Deregulation of miRNA expression is detected in thyroid cancer. Upregulation of miRNAs, such asmiR-146b,miR-221, andmiR-222, is observed in ATC and also in differentiated thyroid cancer (papillary and follicular), indicating that these miRNAs’ overexpression is essential in maintaining tumorigenesis. However, specific miRNAs are downregulated in ATC, such as those of themiR-200andmiR-30families, which are important negative regulators of cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), processes that are overactivated in ATC. Therefore, molecular interference to restore the expression of tumor suppressor miRNAs, or to blunt overexpressed oncogenic miRNAs, is a promising therapeutic approach to ameliorate the treatment of ATC. In this review, we will explore the importance of miRNA deregulation for ATC cell biology.

scholarly journals Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11813
Author(s):  
Jing Wang ◽  
Minxiang Lei ◽  
Zhijie Xu
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Biological Significance ◽  
Protein S ◽  
Gene Expression Omnibus ◽  
Papillary Thyroid ◽  
Migration Ability ◽  
Aberrant Expression ◽  
And Migration

Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Considering the important association between cellular immunity and PTC progression, it is worth exploring the biological significance of immune-related signaling in PTC. Methods Several bioinformatics tools, such as R software, WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), Database for Annotation, Visualization and Integrated Discovery (DAVID), Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to identify the immune-related hub genes in PTC. Furthermore, in vitro experiments were adopted to identify the proliferation and migration ability of PROS1 knockdown groups and control groups in PTC cells. Results The differentially expressed genes (DEGs) of five datasets from Gene Expression Omnibus (GEO) contained 154 upregulated genes and 193 downregulated genes, with Protein S (PROS1) being the only immune-related hub gene. Quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) have been conducted to prove the high expression of PROS1 in PTC. Moreover, PROS1 expression was significantly correlated with lymph nodes classification. Furthermore, knockdown of PROS1 by shRNAs inhibited the cell proliferation and cell migration in PTC cells. Conclusions The findings unveiled the clinical relevance and significance of PROS1 in PTC and provided potential immune-related biomarkers for PTC development and prognosis.

scholarly journals Real-time, high-resolution imaging of tumor cells in genetically engineered and orthotopic models of thyroid cancer

2020 ◽  
Vol 27 (10) ◽  
pp. 529-539
Author(s):  
Xhesika Shanja-Grabarz ◽  
Anouchka Coste ◽  
David Entenberg ◽  
Antonio Di Cristofano
Keyword(s):  
Thyroid Cancer ◽  
High Resolution ◽  
Real Time ◽  
Tumor Cells ◽  
Mouse Models ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Genetically Engineered ◽  
Intravital Imaging ◽  
Anatomical Location

Genetically engineered and orthotopic xenograft mouse models have been instrumental for increasing our understanding of thyroid cancer progression and for the development of novel therapeutic approaches in a setting that is more physiologically relevant than the classical subcutaneous flank implants. However, the anatomical location of the thyroid gland precludes a non-invasive analysis at the cellular level of the interactions between tumor cells and the surrounding microenvironment and does not allow a real-time evaluation of the response of tumor cells to drug treatments. As a consequence, such studies have generally only relied on endpoint approaches, limiting the amount and depth of the information that could be gathered. Here we describe the development of an innovative approach to imaging specific aspects of thyroid cancer biology, based on the implantation of a permanent, minimally invasive optical window that allows high-resolution, multi-day, intravital imaging of the behavior and cellular dynamics of thyroid tumors in the mouse. We show that this technology allows visualization of fluorescently tagged tumor cells both in immunocompetent, genetically engineered mouse models of anaplastic thyroid cancer (ATC) and in immunocompromised mice carrying orthotopic implanted human or mouse ATC cells. Furthermore, the use of recipient mice in which endothelial cells and macrophages are fluorescently labeled allows the detection of the spatial and functional relationship between tumor cells and their microenvironment. Finally, we show that ATC cells expressing a fluorescent biosensor for caspase 3 activity can be effectively utilized to evaluate, in real-time, the efficacy and kinetics of action of novel small molecule therapeutics. This novel approach to intravital imaging of thyroid cancer represents a platform that will allow, for the first time, the longitudinal, in situ analysis of tumor cell responses to therapy and of their interaction with the microenvironment.

scholarly journals The p53-homologue p63 may promote thyroid cancer progression

2005 ◽  
Vol 12 (4) ◽  
pp. 953-971 ◽  
Author(s):  
Roberta Malaguarnera ◽  
Angelo Mandarino ◽  
Emanuela Mazzon ◽  
Veronica Vella ◽  
Piero Gangemi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Human Thyroid ◽  
P53 Family ◽  
Suppressor Activity ◽  
C Terminus ◽  
Thyroid Cancer Cells

Inactivation of p53 and p73 is known to promote thyroid cancer progression. We now describe p63 expression and function in human thyroid cancer. TAp63α is expressed in most thyroid cancer specimens and cell lines, but not in normal thyrocytes. However, in thyroid cancer cells TAp63α fails to induce the target genes (p21Cip1, Bax, MDM2) and, as a consequence, cell cycle arrest and apoptosis occur. Moreover, TAp63α antagonizes the effect of p53 on target genes, cell viability and foci formation, and p63 gene silencing by small interfering (si) RNA results in improved p53 activity. This unusual effect of TAp63α depends on the protein C-terminus, since TAp63β and TAp63γ isoforms, which have a different arrangement of their C-terminus, are still able to induce the target genes and to exert tumour-restraining effects in thyroid cancer cells. Our data outline the existence of a complex network among p53 family members, where TAp63α may promote thyroid tumour progression by inactivating the tumour suppressor activity of p53.

scholarly journals EHF suppresses cancer progression by inhibiting ETS1-mediated ZEB expression

Oncogenesis ◽  
2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Kaname Sakamoto ◽  
Kaori Endo ◽  
Kei Sakamoto ◽  
Kou Kayamori ◽  
Shogo Ehata ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Short Form ◽  
Dominant Negative ◽  
Mesenchymal Transition ◽  
Exon 1 ◽  
Ets Transcription Factor ◽  
Ets Homologous Factor ◽  
Form Variant

AbstractETS homologous factor (EHF) belongs to the epithelium-specific subfamily of the E26 transformation-specific (ETS) transcription factor family. Currently, little is known about EHF’s function in cancer. We previously reported that ETS1 induces expression of the ZEB family proteins ZEB1/δEF1 and ZEB2/SIP1, which are key regulators of the epithelial–mesenchymal transition (EMT), by activating the ZEB1 promoters. We have found that EHF gene produces two transcript variants, namely a long form variant that includes exon 1 (EHF-LF) and a short form variant that excludes exon 1 (EHF-SF). Only EHF-SF abrogates ETS1-mediated activation of the ZEB1 promoter by promoting degradation of ETS1 proteins, thereby inhibiting the EMT phenotypes of cancer cells. Most importantly, we identified a novel point mutation within the conserved ETS domain of EHF, and found that EHF mutations abolish its original function while causing the EHF protein to act as a potential dominant negative, thereby enhancing metastasis in vivo. Therefore, we suggest that EHF acts as an anti-EMT factor by inhibiting the expression of ZEBs, and that EHF mutations exacerbate cancer progression.

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