PLoS ONE：microRNA-7降低FAK表达抑制乳腺癌转移

粘着斑激酶（FAK）是细胞外基质整合素信号以及细胞运动、细胞增殖和细胞存活的重要调节因子。FAK的表达在多种实体瘤中都被证实是明显增加的， FAK表达的增高于肿瘤转移以及患者预后差密切相关。

近日PLoS ONE刊出的一项研究发现miR-7能直接调节FAK的表达。相比于正常乳腺组织，miR-7的表达在恶性肿瘤组织中是减少的，并且miR-7的表达与乳腺癌患者转移成反比。

miR-7的表达上调会增加乳腺癌细胞中E-钙粘蛋白的表达，降低纤维连接蛋白和波形蛋白的表达。miR-7的表达水平与E-cadherin的表达呈正相关，与乳腺癌样本中波形蛋白表达水平呈负相关。

升高侵袭性乳腺癌细胞系中miR-7的表达，能抑制肿瘤细胞的增殖，锚地独立生长能力以及迁移和侵袭能力。相反，抑制HBL-100乳腺上皮细胞株的miR-7表达会促进细胞增殖和锚地独立生长能力。恢复FAK的表达能逆转miR-7抑制乳腺癌细胞迁移和侵袭的能力。 miR-7也能抑制乳腺癌裸鼠移植瘤模型原发性乳腺肿瘤的发展、局部侵袭和转移。因此，转移性乳腺癌中miR-7的表达下降与肿瘤上皮细胞分化水平相关，能抑制转移性肿瘤恶化。

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.