FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway.
FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway.
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FAP-α（成纤维细胞激活蛋白-α）通过FAK途径控制人类乳腺癌细胞系的生长和运动性。
DOI：
10.1186/1471-2121-15-16
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发表时间：
2014-05-21
期刊：
影响因子：
--
通讯作者：
Jiang WG
中科院分区：
文献类型：
--
作者：
Jia J;Martin TA;Ye L;Jiang WG
成纤维细胞活化蛋白α（FAP-α）或seprase是一种整合的膜丝氨酸肽酶。以前的工作并没有令人满意地解释在癌症中观察到的抑制和促进作用。本研究旨在探讨FAP-α在乳腺癌中的作用。在原发性肿瘤样品和细胞系中表征FAP-α的表达，沿着FAP-α表达对体外生长、侵袭、附着和迁移的影响。此外，研究了FAP-α与其他信号通路的潜在相互作用。FAP-α在预后差和生存率低的患者中显著升高。体外实验结果表明，FAP-α过表达的乳腺癌细胞生长能力增强，迁移能力减弱。FAP-α表达对MDA-MB-231细胞的生长、MCF-7细胞和MDA-MB-231细胞的粘附和侵袭能力无明显影响。FAP-α的过表达导致正常培养液和无血清培养液中磷酸化粘着斑激酶（FAK）水平的降低。FAK抑制剂恢复了MCF-7 exp细胞和MDA-MB-231 exp细胞降低的运动能力，并阻止了磷酸化FAK水平的变化。然而，PI 3 K、ERK、PLC β、NWASP、ARP 2/3和ROCK的抑制剂对此没有影响。FAP-α与乳腺癌患者预后不良显著相关。在体外，FAP-α可能通过调节FAK通路促进乳腺癌细胞的增殖并抑制其迁移。这些结果表明FAP-α可能成为未来治疗的目标。
Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCϒ, NWASP, ARP2/3, and ROCK had no influence this. FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies.
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