The interaction between S100A2 and KPNA2 mediates NFYA nuclear import and is a novel therapeutic target for colorectal cancer metastasis
The interaction between S100A2 and KPNA2 mediates NFYA nuclear import and is a novel therapeutic target for colorectal cancer metastasis
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S100A2和KPNA2之间的相互作用介导NFYA核输入，是结直肠癌转移的新治疗靶点
DOI：
10.1038/s41388-021-02116-6
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发表时间：
2021-11-20
期刊：
影响因子：
8
通讯作者：
Zhang, Honghe
中科院分区：
文献类型：
--
作者：
Han, Fengyan;Zhang, Lei;Zhang, Honghe
在癌细胞中，蛋白质的核质运输受到干扰和失调。核孔复合体和货物蛋白是两种主要的运输调节因子。然而，调控肿瘤核质转运的机制仍然不清楚。在这里，我们鉴定了一个S100A2/KPNA2共转运复合体，它在结直肠癌(CRC)中运输肿瘤相关转录因子NFYA。通过S100A2/KNPA2复合体，NFYA通过与S100A2的相互作用被转运到细胞核，抑制E-钙粘蛋白的转录活性，进而促进结直肠癌的转移。特异性抑制剂delanzomib靶向S100A2/KPNA2结合位点是治疗结直肠癌的一种潜在方法。
Nucleocytoplasmic transport of proteins is disrupted and dysregulated in cancer cells. Nuclear pore complexes and cargo proteins are two main transportation regulators. However, the mechanism regulating nucleocytoplasmic transport in cancer remains elusive. Here, we identified a S100A2/KPNA2 cotransport complex that transports the tumor-associated transcription factor NFYA in colorectal cancer (CRC). Through the S100A2/KNPA2 complex, depending on its interaction with S100A2, NFYA is transported to the nucleus and inhibits the transcriptional activity of E-cadherin, which in turn promotes CRC metastasis. Targeting the S100A2/KPNA2 binding sites with the specific inhibitor delanzomib is a potential therapeutic approach for CRC.