Nav1.6 promotes the progression of human follicular thyroid carcinoma cells via JAK-STAT signaling pathway

Li, Haoran; Liu, Jianwei; Fan, Ningning; Wang, Hao; Thomas, Adrian; Yan, Qi; Shen, Li; Qin, Huamin

doi:10.1016/j.prp.2022.153984

Cited by 7 publications

(7 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell progression in knockdown NaV1.5 HSC-3 was reported to be regulated by the Wnt/β-catenin signaling pathway, which also had an influence on cancer cell migration and invasiveness [95][96][97]. In this current study, we saw the effect of SV188 on cell cycle arrest at the G0/G1 phase, which could lead to the inhibition of cell proliferation by inducing cell apoptosis, as observed in previous reports on the induction of apoptosis associated with Nav1.5 and Nav1.6 expression with siRNAs in astrocytoma [98], the expression of neonatal Nav1.5 in human brain astrocytoma, and its effect on the proliferation, invasion, and apoptosis of astrocytoma cells [99] and follicular thyroid carcinoma cells [53]. We also noticed a significant decrease in the mRNA expression of NaV1.7 and NHE-1 and a reduction in cell In this current study, we saw the effect of SV188 on cell cycle arrest at the G0/G1 phase, which could lead to the inhibition of cell proliferation by inducing cell apoptosis, as observed in previous reports on the induction of apoptosis associated with Nav1.5 and Nav1.6 expression with siRNAs in astrocytoma [98], the expression of neonatal Nav1.5 in human brain astrocytoma, and its effect on the proliferation, invasion, and apoptosis of astrocytoma cells [99] and follicular thyroid carcinoma cells [53].…”

Section: Cell Cycle Analysis In Response To Sv188 Treatmentsupporting

confidence: 67%

“…To date, multiple VGSC subtypes have been targeted for the discovery of potential anticancer drugs [15][16][17]40,51,52]. Recently, Na V 1.6 was found to promote human follicular thyroid carcinoma by increasing cell proliferation, epithelial-to-mesenchymal transition, and invasion [53]. However, no such investigation of the sodium channel inhibitors in MTC has been reported since the initial discovery of the presence of sodium channel genes in MTC cells by Klugbauer et al in 1995 [54].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells

Pukkanasut

Whitt

Guenter

et al. 2023

Cancers

View full text Add to dashboard Cite

Our results from quantitative RT-PCR, Western blotting, immunohistochemistry, and the tissue microarray of medullary thyroid cancer (MTC) cell lines and patient specimens confirm that VGSC subtype NaV1.7 is uniquely expressed in aggressive MTC and not expressed in normal thyroid cells and tissues. We establish the druggability of NaV1.7 in MTC by identifying a novel inhibitor (SV188) and investigate its mode of binding and ability to inhibit INa current in NaV1.7. The whole-cell patch-clamp studies of the SV188 in the NaV1.7 channels expressed in HEK-293 cells show that SV188 inhibited the INa current in NaV1.7 with an IC50 value of 3.6 µM by a voltage- and use-dependent blockade mechanism, and the maximum inhibitory effect is observed when the channel is open. SV188 inhibited the viability of MTC cell lines, MZ-CRC-1 and TT, with IC50 values of 8.47 μM and 9.32 μM, respectively, and significantly inhibited the invasion of MZ-CRC-1 cells by 35% and 52% at 3 μM and 6 μM, respectively. In contrast, SV188 had no effect on the invasion of TT cells derived from primary tumor, which have lower basal expression of NaV1.7. In addition, SV188 at 3 μM significantly inhibited the migration of MZ-CRC-1 and TT cells by 27% and 57%, respectively.

show abstract

Section: Cell Cycle Analysis In Response To Sv188 Treatmentsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells

Pukkanasut

Whitt

Guenter

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Therefore, patients with thyroid cancer patients are recommended to undergo p53 gene testing to assess their condition accurately 19 . The JAK/STAT signaling pathway is a pivotal communication hub in cellular activity and crucial in cancer 20 . By interacting with a diverse array of cytokines, the JAK/STAT signaling system affects immune cell differentiation and development by functioning as an immunomodulator.…”

Section: Discussionmentioning

confidence: 99%

“…By interacting with a diverse array of cytokines, the JAK/STAT signaling system affects immune cell differentiation and development by functioning as an immunomodulator. Extensive evidence has demonstrated that the activation of the JAK/STAT signaling promotes the onset and progression of various diseases, including thyroid cancer 20 , 21 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bioinformatics analysis unveils THEMIS2 as a carcinogenic indicator related to immune infiltration and prognosis of thyroid cancer

Liu,

Zou,

Xiang

et al. 2024

Sci Rep

View full text Add to dashboard Cite

The aim of this study was to identify biomarkers associated with the initiation and prognosis of thyroid cancer and elucidate the underlying pathogenic mechanisms. We obtained expression profiles and clinical information from the Cancer Genome Atlas (TCGA)-THCA and three datasets (GSE53157, GSE82208, and GSE76039). The three microarray datasets were combined using Perl and the sva package in R and termed ‘merged dataset’. Weighted gene co-expression network analysis (WGCNA) identified 15 gene co-expression modules in the merged dataset and 235 hub genes. Venn diagram analysis revealed 232 overlapping genes between the merged and THCA datasets. Overlapping genes were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The least absolute shrinkage and selection operator (LASSO) regression identified THEMIS2 as a candidate hub gene. Cox, Kaplan–Meier (K–M) survival and gene set enrichment analysis (GSEA) confirmed the correlation of THEMIS2 with overall survival, its enrichment in immunologic processes, and its association with the p53 and JAK-STAT signaling pathways. Its expression was positively correlated with those of immune checkpoints and the infiltration level of immune cells. Receiver operating characteristic curve (ROC) analysis confirmed that THEMIS2, a diagnostic biomarker, could distinguish between tumor and normal specimens. The nomogram (ROC or DCA) model containing THEMIS2, age, and stage predicted favourable prognoses. Thus, THEMIS2 was a biomarker of immune infiltration and prognosis in thyroid cancer.

show abstract

“…91,95 The activation of the JAK2/STAT3 pathway in follicular thyroid carcinoma (FTC) cells enhanced their proliferation, EMT, and invasion, whereas its inactivation suppressed tumor cell proliferation and promoted apoptosis. 96 The persistent activation of the JAK/STAT signaling pathway accelerated the proliferation and invasion of NPC cells, and the targeting of the key genes of this pathway had an inhibitory effect on tumor cell proliferation, invasion, and metastasis in vitro and in vivo. 97,98 The JAK/STAT pathway is associated with the chemoresistance of tumor cells.…”

mentioning

confidence: 98%

The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma

Li,

Zeng,

Liu

et al. 2023

JIR

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC), which originates in the head or neck tissues, is characterized by high rates of recurrence and metastasis. Inflammation is important in HNSCC prognosis. Inflammatory cells and their secreted factors contribute to the various stages of HNSCC development through multiple mechanisms. In this review, the mechanisms through which inflammatory factors, signaling pathways, and cells contribute to the initiation and progression of HNSCC have been discussed in detail. Furthermore, the diagnostic and therapeutic potential of targeting inflammation in HNSCC has been discussed to gain new insights into improving patient prognosis.

show abstract

Nav1.6 promotes the progression of human follicular thyroid carcinoma cells via JAK-STAT signaling pathway

Cited by 7 publications

References 55 publications

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells

Comprehensive bioinformatics analysis unveils THEMIS2 as a carcinogenic indicator related to immune infiltration and prognosis of thyroid cancer

The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma

Contact Info

Product

Resources

About