Cortactin promotes cell migration and invasion through upregulation of the dedicator of cytokinesis 1 expression in human colorectal cancer
Cortactin promotes cell migration and invasion through upregulation of the dedicator of cytokinesis 1 expression in human colorectal cancer
复制标题
Cortactin 通过上调人结直肠癌中胞质分裂贡献者 1 的表达来促进细胞迁移和侵袭
DOI：
10.3892/or.2016.5058
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发表时间：
2016-10-01
期刊：
影响因子：
4.2
通讯作者：
Zhao, Ren
中科院分区：
文献类型：
--
作者：
Jing, Xiaoqian;Wu, Huo;Zhao, Ren
Cordyn（CTTN）是Src酪氨酸激酶的主要底物，在各种类型的癌症中与细胞增殖、运动和侵袭有关。然而，CTTN驱动的恶性行为的分子机制仍不清楚。本研究通过检测CTTN在大肠癌中的表达，探讨其在大肠癌转移中的作用机制。我们证实了CTTN在淋巴结阳性CRC标本和高侵袭性CRC细胞系中的表达增加。进一步的研究表明，CTTN的过表达促进了CRC细胞的迁移和侵袭，而CTTN沉默抑制了CRC细胞的迁移和侵袭能力。在机制上，CTTN增加胞质分裂贡献因子1（DOCK 1）的表达，并且DOCK 1的基因沉默部分地消除了CTTN的迁移和侵袭能力。我们的研究结果表明，CTTN通过增加DOCK 1表达促进CRC细胞的转移，这可能为结直肠癌治疗提供一个有前途的治疗靶点。
Cortactin (CTTN), a major substrate of the Src tyrosine kinase, has been implicated in cell proliferation, motility and invasion in various types of cancer. However, the molecular mechanisms of CTTN-driven malignant behavior remain unclear. In the current study, we determined the expression of CTTN in colorectal cancer and investigated its underlying mechanism in the metastasis of colorectal cancer. We confirmed increased CTTN expression in lymph node-positive CRC specimens and highly invasive CRC cell lines. Further study has shown that overexpression of CTTN promoted CRC cell migration and invasion, whereas CTTN silencing inhibited CRC cell migratory and invasive capacities in vitro. Mechanistically, CTTN increases expression of dedicator of cytokinesis 1 (DOCK1) and gene silencing of DOCK1 partially abolishes the migration and invasion capacity by CTTN. Our findings indicate that CTTN promotes metastasis of CRC cells by increasing DOCK1 expression and this could offer a promising therapeutic target for colorectal cancer treatment.