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EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity
The EMBO Journal ( IF 11.4 ) Pub Date : 2023-11-13 , DOI: 10.15252/embj.2023113856
Aiguo Tian 1, 2 , Xian-Feng Wang 1 , Yuting Xu 1 , Virginia Morejon 1 , Yi-Chun Huang 1 , Chidi Nwapuda 1 , Wu-Min Deng 1, 2
Affiliation  

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors. Further studies revealed that these distinct multilayering patterns in the follicular epithelium were determined by epidermal growth factor receptor (EGFR) signaling and its downstream target Pointed, a zinc-finger transcription factor. Additionally, we identified Rho kinase as a Pointed target that regulates formation of distinct multilayering patterns. These findings provide insight into how cell polarity genes and receptor tyrosine kinase signaling interact to govern epithelial cell organization and directional growth that contribute to epithelial tumor formation.

中文翻译:

EGFR 信号传导在细胞极性丧失时控制上皮多层形成的方向性

顶端-基底极性由存在于膜连接处的不同蛋白质复合物维持,单层上皮细胞中的极性丧失可导致多层的形成、细胞挤出和/或恶性过度生长。然而,极性丧失如何与内在信号配合来控制对邻近上皮细胞的定向入侵仍然难以捉摸。使用果蝇卵巢滤泡上皮作为模型,我们发现失去致死性巨型幼虫lgl)或大圆盘Dlg)的后卵泡细胞向生殖系细胞顶部聚集,而失去火箭筒Baz)或非典型蛋白激酶的细胞C ( aPKC ) 向野生型邻居的基底侧扩展。进一步的研究表明,滤泡上皮中这些独特的多层模式是由表皮生长因子受体(EGFR)信号传导及其下游靶点(一种锌指转录因子)决定的。此外,我们将Rho 激酶确定为调节不同多层模式形成的定向靶点。这些发现提供了关于细胞极性基因和受体酪氨酸激酶信号如何相互作用以控制上皮细胞组织和定向生长从而促进上皮肿瘤形成的见解。
更新日期:2023-11-13
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