Promotion of Cellular Growth and Motility Is Independent of Enzymatic Activity of Fibroblast Activation Protein-α

作者：Lv, Baobei; Xie, Fei; Zhao, Pengxiang; Ma, Xuemei; Jiang, Wen G.; Yu, Jing; Zhang, Xiaodong; Jia, Jun^*

来源：Cancer Genomics and Proteomics, 2016, 13(3): 201-208.

• Fibroblast activation protein-alpha
• breast cancer
• phosphatidylinositol-3-kinase
• matrix metalloproteinase

Background: Fibroblast activation protein-alpha (FAP alpha) is a type-II integral membrane serine protease and is expressed in most stromal fibroblasts. Recent studies showed that FAP alpha is also expressed in certain cancer cells but its role is still uncertain. Materials and Methods: We analyzed the non-enzymatic activity of FAP alpha in breast cancer cells by introducing an enzymatic mutant FAP alpha (FAPS624A), in which the serine catalytic triad was destroyed. FAP alpha overexpression and knockdown cells were generated as controls. Results: Cellular growth and motility were markedly increased in MCF-7 cells overexpressing FAP alpha and enzymatic-mutant FAPS624A. This is consistent with observations in FAP alpha-silenced BT549 cells. Western blotting showed activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and matrix metalloproteinase (MMP) 2/9 in both wild-type FAP alpha-overexpressing and enzymatic-mutant FAPS624A-overexpressing cells. Conclusion: Promotion of cellular growth and motility is independent of the enzymatic activity of FAP alpha in breast cancer cells. The PI3K/AKT and MMP2/9 signaling pathways might be involved in such regulation.

• 出版日期2016-5
• 单位北京工业大学; 北京大学