TY - JOUR
T1 - Nav1.6 promotes the progression of human follicular thyroid carcinoma cells via JAK-STAT signaling pathway
AU - Li, Haoran
AU - Liu, Jianwei
AU - Fan, Ningning
AU - Wang, Hao
AU - Thomas, Aline M.
AU - Yan, Qiu
AU - Li, Shen
AU - Qin, Huamin
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China ( 82171319 ), Natural Science Foundation of Liaoning Province ( 2019-MS-075 ) and Dalian Medical Science Research Program ( 2012019 ).
Publisher Copyright:
© 2022 Elsevier GmbH
PY - 2022/8
Y1 - 2022/8
N2 - Follicular thyroid carcinoma (FTC) is one of the most common malignant tumors of the endocrine system. Recent studies have shown that voltage-gated sodium channels (VGSCs) affect the proliferation, migration, and invasion of tumor cells. However, the expression and functions of VGSCs, and the molecular pathways activated by VGSCs in FTC cells remain unclear. Our studies revealed that the expression of Nav1.6, encoded by SCN8A, was the predominantly upregulated subtype of VGSCs in FTC tissues. Knockdown of Nav1.6 significantly inhibited the proliferation, epithelial–mesenchymal transition and invasiveness of FTC cells. Using gene set enrichment analysis and Kyoto Encyclopedia of Genes and Genomics, SCN8A was predicted to be related to the JAK-STAT signaling pathway. Hence, we targeted the JAK-STAT pathway and demonstrated that Nav1.6 enhanced FTC cell proliferation, epithelial–mesenchymal transition, and invasion by phosphorylating JAK2 to activate STAT3. Furthermore, downregulating the expression of Nav1.6 improve the susceptibility of FTC cells to ubenimex in vitro. These results suggest Nav1.6 accelerates FTC progression through JAK/STAT signaling and may be a potential target for FTC therapy.
AB - Follicular thyroid carcinoma (FTC) is one of the most common malignant tumors of the endocrine system. Recent studies have shown that voltage-gated sodium channels (VGSCs) affect the proliferation, migration, and invasion of tumor cells. However, the expression and functions of VGSCs, and the molecular pathways activated by VGSCs in FTC cells remain unclear. Our studies revealed that the expression of Nav1.6, encoded by SCN8A, was the predominantly upregulated subtype of VGSCs in FTC tissues. Knockdown of Nav1.6 significantly inhibited the proliferation, epithelial–mesenchymal transition and invasiveness of FTC cells. Using gene set enrichment analysis and Kyoto Encyclopedia of Genes and Genomics, SCN8A was predicted to be related to the JAK-STAT signaling pathway. Hence, we targeted the JAK-STAT pathway and demonstrated that Nav1.6 enhanced FTC cell proliferation, epithelial–mesenchymal transition, and invasion by phosphorylating JAK2 to activate STAT3. Furthermore, downregulating the expression of Nav1.6 improve the susceptibility of FTC cells to ubenimex in vitro. These results suggest Nav1.6 accelerates FTC progression through JAK/STAT signaling and may be a potential target for FTC therapy.
KW - Epithelial–mesenchymal transition
KW - Follicular thyroid carcinoma
KW - JAK-STAT
KW - Nav1.6
KW - Proliferation
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U2 - 10.1016/j.prp.2022.153984
DO - 10.1016/j.prp.2022.153984
M3 - Article
C2 - 35753135
AN - SCOPUS:85132750919
SN - 0344-0338
VL - 236
JO - Pathology Research and Practice
JF - Pathology Research and Practice
M1 - 153984
ER -