Tong Song, Xia Tian, Fan Kai, Jiang Ke, Zhai Wei, Li Jing-Song, Wang Si-Hua, Wang Jian-Jun
Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Exp Cell Res. 2016 Oct 15;348(1):1-9. doi: 10.1016/j.yexcr.2016.08.014. Epub 2016 Aug 21.
14-3-3ζ has been identified as a putative oncogene in several cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms underlying its functions remain undefined. In this study, we show that overexpression of 14-3-3ζ was frequently detected in lung adenocarcinoma (LuAC) tissues and was significantly associated with lymph node metastasis and poor outcome. Functional studies demonstrated that 14-3-3ζ promoted migration and invasion in A549 cells, both of which were effectively inhibited when 14-3-3ζ was silenced with short hairpin RNA (shRNA). Furthermore, 14-3-3ζ-mediated invasion of cancer cells was found to upregulate Snail through the activation of atypical protein kinase C (aPKC). Activation of aPKCζ mediates this effect by stimulating NF-κB signaling. Our results identify a specific pathway by which 14-3-3ζ induces tumor invasion and provide insight into potential therapeutic approaches to target 14-3-3ζ-associated lung adenocarcinoma.
14-3-3ζ已被确定为包括非小细胞肺癌（NSCLC）在内的多种癌症中的一种假定癌基因。然而，其功能背后的机制仍不明确。在本研究中，我们发现14-3-3ζ在肺腺癌（LuAC）组织中经常检测到过表达，并且与淋巴结转移和不良预后显著相关。功能研究表明，14-3-3ζ促进A549细胞的迁移和侵袭，当用短发夹RNA（shRNA）沉默14-3-3ζ时，这两种作用均被有效抑制。此外，发现14-3-3ζ介导的癌细胞侵袭通过激活非典型蛋白激酶C（aPKC）上调Snail。aPKCζ的激活通过刺激NF-κB信号传导介导这种效应。我们的结果确定了14-3-3ζ诱导肿瘤侵袭的特定途径，并为靶向14-3-3ζ相关肺腺癌的潜在治疗方法提供了见解。
