Promotion of Cellular Growth and Motility Is Independent of Enzymatic Activity of Fibroblast Activation Protein-α.
BACKGROUND
Fibroblast activation protein-alpha (FAPα) is a type-II integral membrane serine protease and is expressed in most stromal fibroblasts. Recent studies showed that FAPα is also expressed in certain cancer cells but its role is still uncertain.


METHODS
We analyzed the non-enzymatic activity of FAPα in breast cancer cells by introducing an enzymatic mutant FAPα (FAPS624A), in which the serine catalytic triad was destroyed. FAPα overexpression and knockdown cells were generated as controls.


RESULTS
Cellular growth and motility were markedly increased in MCF-7 cells overexpressing FAPα and enzymatic-mutant FAPS624A. This is consistent with observations in FAPα-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 FAPα-overexpressing and enzymatic-mutant FAPS624A-overexpressing cells.


CONCLUSIONS
Promotion of cellular growth and motility is independent of the enzymatic activity of FAPα in breast cancer cells. The PI3K/AKT and MMP2/9 signaling pathways might be involved in such regulation.
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, P.R. China.
Baobei
B
Lv
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, P.R. China.
Fei
F
Xie
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, P.R. China.
Pengxiang
P
Zhao
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, P.R. China.
Xuemei
X
Ma
Cardiff University-Peking University Joint Cancer Institute, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.
Wen G
WG
Jiang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIP-II Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, P.R. China.
Jing
J
Yu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIP-II Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, P.R. China.
Xiaodong
X
Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIP-II Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, P.R. China vm26jun@gmail.com.
Jun
J
Jia
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
D010450:Endopeptidases; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
Fibroblast activation protein-alpha; breast cancer; matrix metalloproteinase; phosphatidylinositol-3-kinase