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PMID: 24722280 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.

Cell death & disease ·Vol. 5 ·2014-04-10 ·Pages e1155

Wang H, Wu Q, Liu Z, Luo X, Fan Y, Liu Y, Zhang Y, Hua S, Fu Q, Zhao M, Chen Y, Fang W, Lv X

Abstract

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.

MeSH Terms

Animals Carcinoma, Squamous Cell/enzymology,genetics,pathology Cell Cycle/genetics Cell Movement Cell Proliferation Down-Regulation Endopeptidases Epithelial-Mesenchymal Transition/genetics Female Gelatinases/metabolism Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Gene Silencing Humans MAP Kinase Signaling System Male Matrix Metalloproteinases/metabolism Membrane Proteins/metabolism Mice, Nude Middle Aged Mouth Neoplasms/enzymology,genetics,pathology Neoplasm Invasiveness Neoplasm Metastasis PTEN Phosphohydrolase/metabolism Phosphatidylinositol 3-Kinases/metabolism Prognosis Proto-Oncogene Proteins c-akt/metabolism Serine Endopeptidases/metabolism Xenograft Model Antitumor Assays ras Proteins/metabolism

Chemicals

Membrane Proteins Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase PTEN protein, human Endopeptidases Serine Endopeptidases fibroblast activation protein alpha Gelatinases Matrix Metalloproteinases ras Proteins

Authors & Affiliations

13 authors, click to expand affiliations / ORCID

Wang H

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.

Wu Q