Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
PLoS One. 2012;7(8):e41523. doi: 10.1371/journal.pone.0041523. Epub 2012 Aug 2.
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.
黏着斑激酶（FAK）是细胞外基质整合素信号、细胞迁移、细胞增殖和细胞存活的重要介质。在各种实体人类肿瘤中观察到 FAK 表达增加，并且 FAK 表达和活性的增加经常与转移疾病和预后不良相关。在此，我们确定 miR-7 是 FAK 表达的直接调节因子。miR-7 在恶性与正常乳腺组织中的表达降低，其表达与人类乳腺癌患者的转移呈负相关。在乳腺癌细胞中强制表达 miR-7 可增加 E-CADHERIN 的表达，并降低 FIBRONECTIN 和 VIMENTIN 的表达。在乳腺癌样本中，miR-7 的表达水平与 E-CADHERIN mRNA 呈正相关，与 VIMENTIN mRNA 水平呈负相关。在侵袭性乳腺癌细胞系中强制表达 miR-7 可抑制肿瘤细胞单层增殖、锚定非依赖性生长、Matrigel 中的三维生长、迁移和侵袭。相反，在 HBL-100 乳腺上皮细胞系中抑制 miR-7 可促进细胞增殖和锚定非依赖性生长。FAK 表达的挽救逆转了 miR-7 对迁移和侵袭的抑制作用。miR-7 还抑制了原发性乳腺癌的发展、局部侵袭和乳腺癌异种移植物的转移性定植。因此，miR-7 在转移性乳腺癌中的表达降低，与肿瘤上皮分化的水平相关，并抑制转移性进展。
