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胰岛素受体底物4（IRS4）是一种组成型活性致癌驱动因子，与HER2协同作用并导致治疗耐药性。

Insulin receptor substrate 4 (IRS4) is a constitutive active oncogenic driver collaborating with HER2 and causing therapeutic resistance.

作者信息

Ikink Gerjon J, Hilkens John

机构信息

Division of Molecular Genetics, The Netherlands Cancer Institute , Amsterdam, the Netherlands.

出版信息

Mol Cell Oncol. 2017 Jan 17;4(2):e1279722. doi: 10.1080/23723556.2017.1279722. eCollection 2017.

DOI:10.1080/23723556.2017.1279722
PMID:28401183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5383353/
Abstract

Insulin receptor substrate 4 (IRS4) belongs to a family of cytoplasmic docking proteins mediating signals from cell surface receptors to downstream effectors. While IRS1 and IRS2 mediate signals from an active receptor, we found that IRS4 hyperactivates the phosphatidylinositol phosphate kinase (PI3K)-pathway independent of upstream signals and is irresponsive to feedback regulation causing cancer and resistance to human epidermal growth factor receptor 2 (HER2) targeted therapy.

摘要

胰岛素受体底物4（IRS4）属于一类细胞质对接蛋白家族，介导从细胞表面受体到下游效应器的信号。虽然IRS1和IRS2介导来自活性受体的信号，但我们发现IRS4可独立于上游信号过度激活磷脂酰肌醇磷酸激酶（PI3K）途径，并且对导致癌症和对人表皮生长因子受体2（HER2）靶向治疗产生耐药性的反馈调节无反应。

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本文引用的文献

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Nat Commun. 2016 Nov 23;7:13567. doi: 10.1038/ncomms13567.
2
Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking.体细胞拷贝数改变的泛癌分析表明IRS4和IGF2参与增强子劫持。
Nat Genet. 2017 Jan;49(1):65-74. doi: 10.1038/ng.3722. Epub 2016 Nov 21.
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Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway.
Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):556-566. doi: 10.21873/cgp.20405.
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Cancers (Basel). 2023 Sep 20;15(18):4651. doi: 10.3390/cancers15184651.
5
Trastuzumab-resistant breast cancer cells-derived tumor xenograft models exhibit distinct sensitivity to lapatinib treatment in vivo.曲妥珠单抗耐药的乳腺癌细胞衍生的肿瘤异种移植模型在体内对拉帕替尼治疗表现出不同的敏感性。
Biol Proced Online. 2023 Jun 27;25(1):19. doi: 10.1186/s12575-023-00212-3.
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Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns.对印度卵巢癌队列的多组学分析揭示了组织学类型特异性的突变和基因表达模式。
Front Genet. 2023 Apr 6;14:1102114. doi: 10.3389/fgene.2023.1102114. eCollection 2023.
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