Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
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细胞质阿孢素通过调节 TGF-β/Smad2/3 通路促进细胞迁移并提示结直肠癌预后不良
DOI：
10.1038/s41419-019-1376-9
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发表时间：
2019-02-06
影响因子：
9
通讯作者：
Zhang, Shutian
中科院分区：
文献类型：
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作者：
Li, Hengcun;Zhang, Zheng;Zhang, Shutian
以往的研究表明，ASPN作为一种分泌的基质蛋白，在各种类型的癌症的发生中具有潜在的中介作用，但ASPN在癌细胞中的功能仍不清楚。在这里，我们证实了ASPN在结直肠癌（CRC）中的表达水平高于匹配的正常组织，并且25%（2/8）的结直肠癌显示ASPN基因拷贝数变异（CNV）增加/扩增。较高的ASPN表达水平和ASPN CNV增益/扩增均表明CRC患者预后较差。ASPN通过激活Akt/Erk和tgf - β /Smad2/3信号通路，促进CRC细胞增殖、迁移和侵袭，抑制凋亡。进一步的研究发现，ASPN与Smad2/3相互作用，促进Smad2/3易位到细胞核，并上调上皮间质转化（Epithelial-mesenchymal transition， EMT）相关基因的表达。救援试验证实，tgf - β信号在ASPN促进结直肠癌细胞迁移和侵袭的作用中是必不可少的。综上所述，ASPN通过tgf - β /Smad2/3通路促进结直肠癌细胞的迁移和侵袭，可作为结直肠癌患者潜在的预后生物标志物。
Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-beta/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-beta signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-beta/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.