Université Clermont Auvergne, GReD, CNRS UMR 6293, INSERM U1103, 28 place Henri Dunant, BP38, 63001, Clermont-Ferrand, France.
Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, 63009, Clermont-Ferrand, France.
Nat Commun. 2020 May 8;11(1):2300. doi: 10.1038/s41467-020-16123-w.
One of the most important but less understood step of epithelial tumourigenesis occurs when cells acquire the ability to leave their epithelial compartment. This phenomenon, described as basal epithelial cell extrusion (basal extrusion), represents the first step of tumour invasion. However, due to lack of adequate in vivo model, implication of emblematic signalling pathways such as Ras/Mitogen-Activated Protein Kinase (MAPK) and phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathways, is scarcely described in this phenomenon. We have developed a unique model of basal extrusion in the Drosophila accessory gland. There, we demonstrate that both Ras/MAPK and PI3K/AKT/mTOR pathways are necessary for basal extrusion. Furthermore, as in prostate cancer, we show that these pathways are co-activated. This occurs through set up of Epidermal Growth Factor Receptor (EGFR) and Insulin Receptor (InR) dependent autocrine loops, a phenomenon that, considering human data, could be relevant for prostate cancer.
上皮肿瘤发生过程中最重要但理解较少的步骤之一是当细胞获得离开上皮细胞层的能力时。这种现象被描述为基底上皮细胞挤出（基底挤出），是肿瘤侵袭的第一步。然而，由于缺乏足够的体内模型，标志性信号通路（如 Ras/丝裂原活化蛋白激酶（MAPK）和磷酸肌醇 3 激酶（PI3K）/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路）在这种现象中的作用描述甚少。我们在果蝇附属腺中开发了一种独特的基底挤出模型。在那里，我们证明了 Ras/MAPK 和 PI3K/AKT/mTOR 通路对于基底挤出都是必需的。此外，与前列腺癌一样，我们表明这些通路被共同激活。这是通过表皮生长因子受体（EGFR）和胰岛素受体（InR）依赖性自分泌环的建立来实现的，考虑到人类数据，这种现象可能与前列腺癌相关。
