Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.
It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC.
1] Department of Stomatology of Nanfang Hospital, Southern Medical University, Guangzhou, PR China [2] Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Wang
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Wu
1] Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China [2] Department of Pathology, School of Basic Medicine, Guangzhou Medical University, Guangzhou, PR China.
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Liu
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Luo
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Fan
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Liu
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Zhang
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Hua
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Fu
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Zhao
Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Chen
1] Department of Stomatology of Nanfang Hospital, Southern Medical University, Guangzhou, PR China [2] Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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Fang
1] Department of Stomatology of Nanfang Hospital, Southern Medical University, Guangzhou, PR China [2] Cancer Research Institute, School of Basic Medicine, Southern Medical University, Guangzhou, PR China.
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D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D010450:Endopeptidases; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
D010450:Endopeptidases; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D008565:Membrane Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012697:Serine Endopeptidases; D018631:ras Proteins; D000099167:Fibroblast Activation Protein Alpha; C494929:PTEN protein, human