Asporin enhances colorectal cancer metastasis through activating the EGFR/src/cortactin signaling pathway.
Asporin enhances colorectal cancer metastasis through activating the EGFR/src/cortactin signaling pathway.
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DOI：
10.18632/oncotarget.12336
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Zhao R
中科院分区：
文献类型：
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作者：
Wu H;Jing X;Cheng X;He Y;Hu L;Wu H;Ye F;Zhao R
Asporin作为一种致癌基因参与了多种人类癌症的发生发展，但其在结直肠癌发生发展中的作用尚未明确。在临床标本中，我们发现asporin在结直肠癌组织中的表达高于癌旁正常组织，并且asporin的表达水平与患者的淋巴结转移状况和TNM分期显著相关。通过在大肠癌细胞系RKO和SW 620中敲低asporin或在大肠癌细胞系HT-29和LoVo中过表达asporin，我们发现asporin可以增强大肠癌细胞的伤口愈合、迁移和侵袭能力。进一步通过人脐静脉内皮细胞（HUVECs）管形成实验和异种移植模型，发现asporin通过刺激VEGF信号通路促进肿瘤生长。门静脉注射模型显示asporin过表达促进了HT 29细胞的肝转移，而asporin敲低抑制了RKO细胞的肝转移。此外，asporin还可增强EGFR/Src/corpine信号通路的磷酸化，这可能是asporin参与结直肠癌转移的生物学机制之一。这些结果提示asporin促进了大肠癌的生长和转移，可能成为大肠癌治疗的新靶点。
Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells. Further more, with the human umbilical vein endothelial cells (HUVECs) tube formation assays and the xenograft model, we found that asporin promoted the tumor growth through stimulating the VEGF signaling pathway. The portal vein injection models suggested that asporin overexpression stimulated the liver metastasis of HT29 cell line, while asporin knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin was found to augment the phosphorylation of EGFR/Src/cortactin signaling pathway, which might be contributed to the biological functions of asporin in CRC metastasis. These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future.