2012年8月13日 訊 /生物谷BIOON/ --粘著斑激酶（FAK）是細(xì)胞外基質(zhì)整合素信號以及細(xì)胞運(yùn)動、細(xì)胞增殖和細(xì)胞存活的重要調(diào)節(jié)因子,。FAK的表達(dá)在多種實(shí)體瘤中都被證實(shí)是明顯增加的， FAK表達(dá)的增高于腫瘤轉(zhuǎn)移以及患者預(yù)后差密切相關(guān),。
近日PLoS ONE刊出的一項研究發(fā)現(xiàn)miR-7能直接調(diào)節(jié)FAK的表達(dá),。相比于正常乳腺組織，miR-7的表達(dá)在惡性腫瘤組織中是減少的,，并且miR-7的表達(dá)與乳腺癌患者轉(zhuǎn)移成反比,。
miR-7的表達(dá)上調(diào)會增加乳腺癌細(xì)胞中E-鈣粘蛋白的表達(dá)，降低纖維連接蛋白和波形蛋白的表達(dá),。miR-7的表達(dá)水平與E-cadherin的表達(dá)呈正相關(guān),，與乳腺癌樣本中波形蛋白表達(dá)水平呈負(fù)相關(guān)。
升高侵襲性乳腺癌細(xì)胞系中miR-7的表達(dá),，能抑制腫瘤細(xì)胞的增殖,，錨地獨(dú)立生長能力以及遷移和侵襲能力。相反,，抑制HBL-100乳腺上皮細(xì)胞株的miR-7表達(dá)會促進(jìn)細(xì)胞增殖和錨地獨(dú)立生長能力,。恢復(fù)FAK的表達(dá)能逆轉(zhuǎn)miR-7抑制乳腺癌細(xì)胞遷移和侵襲的能力,。 miR-7也能抑制乳腺癌裸鼠移植瘤模型原發(fā)性乳腺腫瘤的發(fā)展,、局部侵襲和轉(zhuǎn)移,。因此，轉(zhuǎn)移性乳腺癌中miR-7的表達(dá)下降與腫瘤上皮細(xì)胞分化水平相關(guān),，能抑制轉(zhuǎn)移性腫瘤惡化,。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0041523
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MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
Xiangjun Kong1#, Gaopeng Li1#, Yan Yuan1, Yan He1, Xiaoli,et al.
Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression.
