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DPYSL2 interacts with JAK1 to mediate breast cancer cell migration
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2022-05-16 , DOI: 10.1083/jcb.202106078
Areej Abu Rmaileh 1 , Balakrishnan Solaimuthu 1 , Anees Khatib 1 , Shirel Lavi 1 , Mayur Tanna 1 , Arata Hayashi 1 , Michal Ben Yosef 1 , Michal Lichtenstein 1 , Nir Pillar 2 , Yoav D Shaul 1
Affiliation  

The intricate neuronal wiring during development requires cytoskeletal reorganization orchestrated by signaling cues. Because cytoskeletal remodeling is a hallmark of cell migration, we investigated whether metastatic cancer cells exploit axon guidance proteins to migrate. Indeed, in breast cancer patients, we found a significant correlation between mesenchymal markers and the expression of dihydropyrimidinase-like 2 (DPYSL2), a regulator of cytoskeletal dynamics in growing axons. Strikingly, DPYSL2 knockout in mesenchymal-like breast cancer cells profoundly inhibited cell migration, invasion, stemness features, tumor growth rate, and metastasis. Next, we decoded the molecular mechanism underlying this phenomenon and revealed an interaction between DPYSL2 and Janus kinase 1 (JAK1). This binding is crucial for activating signal transducer and activator of transcription 3 (STAT3) and the subsequent expression of vimentin, the promigratory intermediate filament. These findings identify DPYSL2 as a molecular link between oncogenic signaling pathways and cytoskeletal reorganization in migrating breast cancer cells.

中文翻译:

DPYSL2 与 JAK1 相互作用介导乳腺癌细胞迁移

发育过程中复杂的神经元接线需要通过信号线索协调的细胞骨架重组。由于细胞骨架重塑是细胞迁移的标志,我们研究了转移性癌细胞是否利用轴突引导蛋白进行迁移。事实上,在乳腺癌患者中,我们发现间充质标记物与二氢嘧啶酶样 2 (DPYSL2) 的表达之间存在显着相关性,DPYSL2 是轴突生长中细胞骨架动力学的调节因子。引人注目的是,间充质样乳腺癌细胞中的 DPYSL2 敲除可显着抑制细胞迁移、侵袭、干性特征、肿瘤生长速度和转移。接下来,我们解码了这一现象背后的分子机制,并揭示了 DPYSL2 和 Janus 激酶 1 (JAK1) 之间的相互作用。这种结合对于激活信号转导子和转录激活子 3 (STAT3) 以及随后的波形蛋白(前移中间丝)的表达至关重要。这些发现确定 DPYSL2 是乳腺癌细胞迁移中致癌信号通路和细胞骨架重组之间的分子联系。
更新日期:2022-05-16
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