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.
Highlights
Fibroblast Activation Protein, Alpha (FAP) is a homodimeric integral membrane gelatinase belonging to the serine protease family
Increased expression of FAP is unfavorable for oral squamous cell carcinoma (OSCC) prognosis
Protein expression levels of FAP were measured in samples of 84 archived paraffin-embedded OSCC tissues and 12 non-cancerous oral cavity epithelium tissues using immunohistochemical staining (Figure 1–Ia–h)
Summary
Fibroblast Activation Protein, Alpha (FAP) is a homodimeric integral membrane gelatinase belonging to the serine protease family. FAP was found to be selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. Exogenous FAP protein expression or FAP-overexpressing fibroblasts promoted cell proliferation and invasion in ovarian cancer and pancreatic cancer.[8,9]. Several investigations have indicated that FAP is expressed in epithelium-derived tumor cells including breast cancer,[10] pancreatic cancer,[11] gastric cancer,[12] colorectal cancer,[13] and cervical cancer[14] and its elevated expression as an unfavorable factor promotes the poor progression for these cancers. This study was designed to investigate the function and possible molecular basis of FAP in the pathogenesis of OSCC. We demonstrated that FAP exerts an impact as a potential oncogene, which in turn contributes to the initiation and progression of OSCC
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