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A novel functional crosstalk between DDR1 and the IGF axis and its relevance for breast cancer.
Cell Adhesion & Migration ( IF 3.2 ) Pub Date : 2018-03-01 , DOI: 10.1080/19336918.2018.1445953
Antonino Belfiore 1 , Roberta Malaguarnera 2 , Maria Luisa Nicolosi 2 , Rosamaria Lappano 3 , Marco Ragusa 4 , Andrea Morrione 5 , Veronica Vella 1, 6
Affiliation  

In the last decades increasing importance has been attributed to the Insulin/Insulin-like Growth Factor signaling (IIGFs) in cancer development, progression and resistance to therapy. In fact, IIGFs is often deregulated in cancer. In particular, the mitogenic insulin receptor isoform A (IR-A) and the insulin-like growth factor receptor (IGF-1R) are frequently overexpressed in cancer together with their cognate ligands IGF-1 and IGF-2. Recently, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis. Herein, we review recent findings indicating that DDR1 is as a novel modulator of IR and IGF-1R expression and function. DDR1 functionally interacts with IR and IGF-1R and enhances the biological actions of insulin, IGF-1 and IGF-2. Conversely, DDR1 is upregulated by IGF-1, IGF-2 and insulin through the PI3K/AKT/miR-199a-5p circuit. Furthermore, we discuss the role of the non-canonical estrogen receptor GPER1 in the DDR1-IIGFs crosstalk. These data suggest a wider role of DDR1 as a regulator of cell response to hormones, growth factors, and signals coming from the extracellular matrix.

中文翻译:

DDR1和IGF轴之间的新型功能性串扰及其与乳腺癌的相关性。

在过去的几十年中,胰岛素/类胰岛素生长因子信号转导(IIGF)在癌症发展,进展和对治疗的抵抗力中的重要性日益增加。实际上,IIGFs在癌症中常常被放松调节。特别是,促有丝分裂的胰岛素受体同工型A(IR-A)和胰岛素样生长因子受体(IGF-1R)在癌中经常与其同源配体IGF-1和IGF-2一起过表达。最近,我们确定了盘状蛋白结构域受体1(DDR1)作为一种新的IR-A相互作用蛋白。DDR1是一种非整合素胶原酪氨酸激酶受体,在几种恶性肿瘤中均过表达,并在癌症的进展和转移中发挥作用。在本文中,我们回顾了最近的发现,表明DDR1是IR和IGF-1R表达和功能的新型调节剂。DDR1在功能上与IR和IGF-1R相互作用,并增强胰岛素,IGF-1和IGF-2的生物学作用。相反,DDR1通过PI3K / AKT / miR-199a-5p电路被IGF-1,IGF-2和胰岛素上调。此外,我们讨论了非典型雌激素受体GPER1在DDR1-IIGFs串扰中的作用。这些数据表明,DDR1在调节细胞对激素,生长因子和来自细胞外基质的信号的反应中起着更广泛的作用。
更新日期:2019-11-01
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