The CXCL12–CXCR4 axis promotes migration, invasiveness, and EMT in human papillary thyroid carcinoma B-CPAP cells via NF-κB signaling

2018 ◽  
Vol 96 (5) ◽  
pp. 619-626 ◽  
Author(s):  
Yuanqiang Lin ◽  
Qingjie Ma ◽  
Lin Li ◽  
Hui Wang
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Cxc Chemokine ◽  
Chemokine Ligand ◽  
Cxcr4 Axis

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy involving local and distant metastasis. It is known that CXC chemokine ligand 12 (CXCL12) interacts specifically with CXC chemokine receptor 4 (CXCR4) to guide the migration of PTC cells. However, the signaling pathway downstream of the CXCL12–CXCR4 axis in PTC is not fully understood. In the present study, high expression of CXCR4 was detected in 38 out of 82 specimens of PTC, and the expression level of CXCR4 significantly correlated with the stage of PTC. Additionally, the roles of the CXCL12–CXCR4 axis in the migration, invasion, and epithelial–mesenchymal transition (EMT) of B-CPAP cells were investigated in vitro. The motility and invasiveness were significantly enhanced in CXCR4-overexpressing B-CPAP cells with CXCL12 treatment. Moreover, the CXCL12–CXCR4 axis promoted the EMT process, as evidenced by a decreased level of E-cadherin and increased expressions of N-cadherin and vimentin. Furthermore, the CXCL12–CXCR4 axis activated the nuclear factor kappa-B (NF-κB) signaling pathway, whereas BAY11-7082, an IκB phosphorylation inhibitor, counteracted CXCL12–CXCR4-induced migration, invasion, and EMT processes in B-CPAP cells. In conclusion, the CXCL12–CXCR4 axis promotes the migration, invasion, and EMT processes in B-CPAP cells, at least partly, by activating the NF-κB signaling pathway.

scholarly journals MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yonglian Huang ◽  
Hengwei Zhang ◽  
Lidong Wang ◽  
Chenxi Liu ◽  
Mingyue Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract Background Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. Methods qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial–mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. Results In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. Conclusion Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

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.

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