scholarly journals miR-199b-5p-Stonin 2 axis regulates metastases and epithelial-to-mesenchymal transition of papillary thyroid carcinoma

IUBMB Life ◽  
2018 ◽  
Vol 71 (1) ◽  
pp. 28-40 ◽  
Author(s):  
Lei Ren ◽  
Yapei Xu ◽  
Guijun Qin ◽  
Cong Liu ◽  
Yushan Yan ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Stonin 2

scholarly journals A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression

2011 ◽  
Vol 19 (1) ◽  
pp. 39-55 ◽  
Author(s):  
Sonia D'Inzeo ◽  
Arianna Nicolussi ◽  
Caterina Francesca Donini ◽  
Massimo Zani ◽  
Patrizia Mancini ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Papillary Thyroid ◽  
Tgfβ Signaling ◽  
Strong Reduction ◽  
Mesenchymal Transition ◽  
Wide Range

Smad proteins are the key effectors of the transforming growth factor β (TGFβ) signaling pathway in mammalian cells. Smad4 plays an important role in human physiology, and its mutations were found with high frequency in wide range of human cancer. In this study, we have functionally characterized Smad4 C324Y mutation, isolated from a nodal metastasis of papillary thyroid carcinoma. We demonstrated that the stable expression of Smad4 C324Y in FRTL-5 cells caused a significant activation of TGFβ signaling, responsible for the acquisition of transformed phenotype and invasive behavior. The coexpression of Smad4 C324Y with Smad4 wild-type determined an increase of homo-oligomerization of Smad4 with receptor-regulated Smads and a lengthening of nuclear localization. FRTL-5 clones overexpressing Smad4 C324Y showed a strong reduction of response to antiproliferative action of TGFβ1, acquired the ability to grow in anchorage-independent conditions, showed a fibroblast-like appearance and a strong reduction of the level of E-cadherin, one crucial event of the epithelial–mesenchymal transition process. The acquisition of a mesenchymal phenotype gave the characteristics of increased cellular motility and a significant reduction in adhesion to substrates such as fibronectin and laminin. Overall, our results demonstrate that the Smad4 C324Y mutation plays an important role in thyroid carcinogenesis and can be considered as a new prognostic and therapeutic target for thyroid cancer.

scholarly journals Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weilin Pu ◽  
Xiao Shi ◽  
Pengcheng Yu ◽  
Meiying Zhang ◽  
Zhiyan Liu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Single Cell ◽  
Epithelial Mesenchymal Transition ◽  
Distant Metastases ◽  
Developmental Trajectory ◽  
Papillary Thyroid ◽  
Normal Morphology ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

AbstractThe tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.

scholarly journals CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3042 ◽  
Author(s):  
Young Mun Jeong ◽  
Haejin Cho ◽  
Tae-Min Kim ◽  
Yourha Kim ◽  
Sora Jeon ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
High Expression ◽  
Migration And Invasion ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Tumor Immune Escape ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Cd73 Expression

CD73 is involved in tumor immune escape and promotes the growth and progression of cancer cells. The functional role of CD73 expression in papillary thyroid carcinoma (PTC) has not yet been established. In 511 patients with PTC, immunohistochemistry for CD73 on tissue microarrays showed that the high expression of CD73 was associated with an aggressive histologic variant (p = 0.002), extrathyroidal extension (p < 0.001), lymph node metastasis (p < 0.001), and BRAFV600E mutation (p = 0.015). Survival analysis results showed that patients with high CD73 expression had worse recurrence-free survival (p = 0.023). CD73 inhibitors induced G1 cell cycle arrest and apoptosis, inhibited the migration and invasion of PTC cells, and suppressed tumor growth in PTC xenograft nude mice. High expression of CD73 (NT5E) mRNA was associated with unfavorable clinicopathologic characteristics, the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes in The Cancer Genome Atlas (TCGA) dataset. Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73–adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.

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