近日,
据研究人员介绍,动物已经进化出一些机制,如细胞竞争,进而从一个组织中清除危险或无功能的细胞。肿瘤坏死因子信号传导可以从果蝇的成虫上皮细胞中消除克隆性恶性肿瘤,但为什么这一途径在肿瘤细胞中被激活,而不是在正常组织中被激活,目前尚不清楚。
Title: Epithelial monitoring through ligand-receptor segregation ensures malignant cell elimination
Author: Geert de Vreede, Stephan U. Gerlach, David Bilder
Issue&Volume: 2022-04-15
Abstract: Animals have evolved mechanisms, such as cell competition, to remove dangerous or nonfunctional cells from a tissue. Tumor necrosis factor signaling can eliminate clonal malignancies from Drosophila imaginal epithelia, but why this pathway is activated in tumor cells but not normal tissue is unknown. We show that the ligand that drives elimination is present in basolateral circulation but remains latent because it is spatially segregated from its apically localized receptor. Polarity defects associated with malignant transformation cause receptor mislocalization, allowing ligand binding and subsequent apoptotic signaling. This process occurs irrespective of the neighboring cells’ genotype and is thus distinct from cell competition. Related phenomena at epithelial wound sites are required for efficient repair. This mechanism of polarized compartmentalization of ligand and receptor can generally monitor epithelial integrity to promote tissue homeostasis.
DOI: abl4213
Source: https://www.science.org/doi/10.1126/science.abl4213