Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA.
Life Sci Alliance. 2022 Jul 8;5(11). doi: 10.26508/lsa.202201470. Print 2022 Nov.
Clustering of supernumerary centrosomes, which potentially leads to cell survival and chromosomal instability, is frequently observed in cancers. However, the molecular mechanisms that control centrosome clustering remain largely unknown. The centrosomal kinesin KIF24 was previously shown to restrain the assembly of primary cilia in mammalian cells. Here, we revealed that KIF24 depletion suppresses multipolar spindle formation by clustering centrosomes in pancreatic ductal adenocarcinoma (PDAC) cells harboring supernumerary centrosomes. KIF24 depletion also induced hyper-proliferation and improved mitotic progression in PDAC cells. In contrast, disruption of primary cilia failed to affect the proliferation and spindle formation in KIF24-depleted cells. These results suggest a novel role for KIF24 in suppressing centrosome clustering independent of primary ciliation in centrosome-amplified PDAC cells.
多余中心体的聚集，可能导致细胞存活和染色体不稳定性，在癌症中经常观察到。然而，控制中心体聚集的分子机制在很大程度上仍然未知。中心体驱动蛋白 KIF24 先前被证明可以抑制哺乳动物细胞中初级纤毛的组装。在这里，我们揭示了 KIF24 的耗竭通过聚集胰腺导管腺癌 (PDAC) 细胞中的中心体来抑制多极纺锤体的形成，这些细胞具有多余的中心体。KIF24 的耗竭也诱导了 PDAC 细胞的过度增殖和有丝分裂进程的改善。相比之下，破坏初级纤毛并没有影响 KIF24 耗竭细胞的增殖和纺锤体形成。这些结果表明 KIF24 在抑制中心体聚集方面具有新的作用，该作用独立于中心体扩增的 PDAC 细胞中的初级纤毛形成。
