IRS1通过EMT和PI3K/AKT途径促进甲状腺癌转移。

IF 3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Fang Yu, Dongdong Huang, Yeye Kuang, Jian Dong, Qingmei Han, Jie Zhou, Xiaodong Teng
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引用次数: 0

摘要

目的:胰岛素受体亚组分 1(IRS1)蛋白是胰岛素样生长因子-1 受体及其家族成员向 IRS1 下游蛋白进行胞外信号转导的重要信号转导适配器。据报道,IRS1 参与了一些实体瘤的肿瘤发生和转移。研究IRS1在甲状腺癌中的作用有助于在初诊时筛查高危患者:免疫组化法检测131例转移性甲状腺癌组织中IRS1的表达水平。采用伤口愈合、细胞侵袭和集落形成试验研究IRS1在体外的功能。通过RNA测序(RNA-seq)和Western印迹分析,研究IRS1在甲状腺癌细胞中的潜在调控机制:结果:IRS1在甲状腺癌中高表达,其表达与远处转移和晚期临床分期呈正相关。体外研究表明,IRS1是甲状腺癌细胞迁移、侵袭和集落形成的重要介质。RNA-seq显示,IRS1通过调控上皮-间质转化和磷酸肌酸3-激酶(PI3K)/AKT通路促进甲状腺癌的转移:结论:IRS1的过表达会导致甲状腺癌的侵袭性,有望成为甲状腺癌的分层标志物和潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways

Objective

Insulin receptor substract 1 (IRS1) protein is an important signal transduction adapter for extracellular signal transduction from insulin-like growth factor-1 receptor and its family members to IRS1 downstream proteins. IRS1 has been reported to be involved in tumourigenesis and metastasis in some of solid tumors. Investigating the role of IRS1 in thyroid cancer can help to screen high risk patients at the initial diagnosis.

Design, Patients and Measurements

Immunohistochemical assay was used to detect the expression levels of IRS1 in 131 metastatic thyroid cancer tissues. Wound healing, cell invasion and colony formation assays were used to study the functions of IRS1 in vitro. RNA sequencing (RNA-seq) and Western blot analysis analyses were performed to examine the underlying regulation mechanisms of IRS1 in thyroid cancer cells.

Results

IRS1 was highly expressed in thyroid cancers and its expression was positively associated with distant metastasis and advanced clinical stages. In vitro studies demonstrated that IRS1 is an important mediator of migration, invasion and colony formation of thyroid cancer cells. RNA-seq showed that IRS1 promoted the metastasis of thyroid cancer by regulating epithelial-mesenchymal transition and phosphoinositide 3-kinase (PI3K)/AKT pathway.

Conclusions

IRS1 overexpression contributes to the aggressiveness of thyroid cancer and is expected to be a stratified marker and a potential therapeutic target for thyroid cancer.

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来源期刊
Clinical Endocrinology
Clinical Endocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
3.10%
发文量
192
审稿时长
1 months
期刊介绍: Clinical Endocrinology publishes papers and reviews which focus on the clinical aspects of endocrinology, including the clinical application of molecular endocrinology. It does not publish papers relating directly to diabetes care and clinical management. It features reviews, original papers, commentaries, correspondence and Clinical Questions. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.
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