Ricolo Delia, Deligiannaki Myrto, Casanova Jordi, Araújo Sofia J
Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Cientific de Barcelona, Carrer de Baldiri Reixac 10, 08028 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Carrer de Baldiri Reixac 10, 08028 Barcelona, Spain.
Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Cientific de Barcelona, Carrer de Baldiri Reixac 10, 08028 Barcelona, Spain.
Curr Biol. 2016 Oct 24;26(20):2805-2813. doi: 10.1016/j.cub.2016.08.020. Epub 2016 Sep 29.
Centrosome amplification is a hallmark of cancer, although we are still far from understanding how this process affects tumorigenesis [1, 2]. Besides the contribution of supernumerary centrosomes to mitotic defects, their biological effects in the post-mitotic cell are not well known. Here, we exploit the effects of centrosome amplification in post-mitotic cells during single-cell branching. We show that Drosophila tracheal cells with extra centrosomes branch more than wild-type cells. We found that mutations in Rca1 and CycA affect subcellular branching, causing tracheal tip cells to form more than one subcellular lumen. We show that Rca1 and CycA post-mitotic cells have supernumerary centrosomes and that other mutant conditions that increase centrosome number also show excess of subcellular lumen branching. Furthermore, we show that de novo lumen formation is impaired in mutant embryos with fewer centrioles. The data presented here define a requirement for the centrosome as a microtubule-organizing center (MTOC) for the initiation of subcellular lumen formation. We propose that centrosomes are necessary to drive subcellular lumen formation. In addition, centrosome amplification increases single-cell branching, a process parallel to capillary sprouting in blood vessels [3]. These results shed new light on how centrosomes can contribute to pathology independently of mitotic defects.
中心体扩增是癌症的一个标志，尽管我们距离理解这一过程如何影响肿瘤发生仍有很大差距[1,2]。除了多余的中心体对有丝分裂缺陷的影响外，它们在有丝分裂后细胞中的生物学效应尚不清楚。在这里，我们利用单细胞分支过程中有丝分裂后细胞中中心体扩增的效应。我们发现，具有额外中心体的果蝇气管细胞比野生型细胞分支更多。我们发现Rca1和CycA中的突变影响亚细胞分支，导致气管顶端细胞形成不止一个亚细胞管腔。我们表明，Rca1和CycA有丝分裂后细胞具有多余的中心体，并且其他增加中心体数量的突变条件也显示出亚细胞管腔分支过多。此外，我们表明在中心粒较少的突变胚胎中，从头形成管腔受到损害。这里呈现的数据定义了中心体作为微管组织中心（MTOC）对于亚细胞管腔形成起始的需求。我们提出中心体对于驱动亚细胞管腔形成是必要的。此外，中心体扩增增加单细胞分支，这一过程与血管中的毛细血管发芽平行[3]。这些结果为中心体如何独立于有丝分裂缺陷而导致病理学提供了新的线索。
