CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway.
CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway.
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DOI：
10.1371/journal.pone.0112908
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yan M
中科院分区：
文献类型：
--
作者：
Zang M;Zhang B;Zhang Y;Li J;Su L;Zhu Z;Gu Q;Liu B;Yan M
CEACAM 6在肿瘤组织中的过表达在多种人类癌症的侵袭、转移和抗失巢凋亡中起重要作用。我们最近报道CEACAM 6在胃癌组织中表达上调，并促进胃癌转移。在这里，我们报告，CEACAM 6促进腹膜转移在体内，并呈负相关，在GC组织中的E-钙粘蛋白的表达。过表达的CEACAM 6在GC中诱导上皮-间质转化（EMT），如通过EMT标志物N-钙粘蛋白、波形蛋白和Slug的增加所测量的，而在CEACAM 6过表达的GC细胞中E-钙粘蛋白表达降低;在CEACAM 6沉默的细胞中观察到相反的结果。胃癌组织中E-cadherin的表达与肿瘤浸润深度、淋巴结转移及TNM分期呈负相关。此外，CEACAM 6还能提高胃癌组织中基质金属蛋白酶-9（MMP-9）的活性，抗MMP-9抗体可逆转CEACAM 6诱导的胃癌细胞侵袭和迁移能力的增强。CEACAM 6还增加了磷酸化AKT的水平，这与多种人类肿瘤的进展有关。我们进一步观察到，PI 3 K抑制剂LY 294002可以通过间质-上皮转化逆转CEACAM 6诱导的EMT。这些发现表明CEACAM 6通过PI 3 K/AKT信号通路促进EMT而增强GC的侵袭和转移。
Overexpressed CEACAM6 in tumor tissues plays important roles in invasion, metastasis and anoikis resistance in a variety of human cancers. We recently reported that CEACAM6 expression is upregulated in Gastric cancer (GC) tissues and promoted GC metastasis. Here, we report that CEACAM6 promotes peritoneal metastases in vivo and is negatively correlated with E-cadherin expression in GC tissues. Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells. Furthermore, E-cadherin expression was negatively correlated with depth of tumor invasion, lymph node metastasis and TNM stage in GC tissues. Additionally, CEACAM6 elevated matrix metalloproteinase-9 (MMP-9) activity in GC, and anti-MMP-9 antibody could reverse the increasing invasion and migration induced by CEACAM6. CEACAM6 also increased the levels of phosphorylated AKT, which is involved in the progression of a variety of human tumors. We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition. These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.
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影响因子：
8
作者：
Duxbury, MS;Ito, H;Whang, EE
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Biglycan通过激活FAK信号通路增强胃癌侵袭能力
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