Fibroblast activation protein-α promotes ovarian cancer cell proliferation and invasion via extracellular and intracellular signaling mechanisms

Yang, Weiwei; Han, Wei; Ye, Shengqian; Liu, DuanYang; Wu, Jun; Liu, Hongyu; Li, Chunhong; Chen, He

doi:10.1016/j.yexmp.2013.06.007

Cited by 39 publications

(19 citation statements)

References 23 publications

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“…In this study, we also observed the inactivation of pMEK and pERK after knocking down FAP in OSCC cells compared with control cells. This result is similar to Yang et al 's report 8 and suggested that ERK signaling positively mediates FAP-stimulated cell growth and the EMT program.…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 92%

“…Exogenous FAP protein expression or FAP-overexpressing fibroblasts promoted cell proliferation and invasion in ovarian cancer and pancreatic cancer. 8, 9 …”

mentioning

confidence: 99%

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

et al. 2014

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“…It is also highly expressed in cancer cells and has been demonstrated to have pro-tumorigenic activity. 6,7 Some studies 8,10,9 indicated that FAP can induce EMT in various human cancers. However, the exact mechanism of FAP in EMT and OSCC carcinogenesis is still unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>Fibroblast Activation Protein (FAP) Overexpression Induces Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma by Down-Regulating Dipeptidyl Peptidase 9 (DPP9)</p>

Wu¹,

Zhao²,

Huang³

et al. 2020

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Purpose: Fibroblast activation protein (FAP) acts as a tumor promoter via epithelialmesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the FAP targeting proteins and explore the precise mechanism by which FAP promotes EMT in OSCC. Patients and Methods: Proteins interacting with FAP were found and filtered by immunoprecipitation-mass spectrometry (IP-MS). Both DPP9 protein and mRNA were examined in 90 paired OSCC samples and matched normal tissue. DPP9 knockdown was conducted to determine its function in OSCC in vitro and in vivo. Results: Dipeptidyl peptidase 9 (DPP9) was identified as interacting with FAP intracellularly by IP-MS. The levels of both DPP9 protein and mRNA were down-regulated in OSCC tissue. Lower DPP9 expression was correlated with unfavorable survival rates of OSCC patients. DPP9 knockdown accelerates the proliferation of OSCC cells in vitro and in vivo. Overexpression of FAP leads to a reduction in DPP9 expression. Likewise, DPP9 overexpression reverses the proliferation, migration, invasion and EMT induced by FAP during OSCC. Conclusion: Our study finds that FAP promotes EMT of OSCC by down-regulating DPP9 in a non-enzymatic manner. FAP-DPP9 pathway could be a potential therapeutic target of OSCC.

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“…Tumor-promoting or -suppressing effects of FAPa expression are conversely discussed (Ariga et al, 2001;Cheng et al, 2002;Huang et al, 2004;Ramirez-Montagut et al, 2004;Cheng et al, 2005). Several studies have been based on altered FAPa expression in tumor cells, including ovarian cancer cells (Yang et al, 2013b), breast cancer cells (Huang et al, 2011b) and human embryonic kidney cells (Cheng et al, 2005). These settings do however not address the rather stromal expression of FAPa.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast activation protein‐α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations

et al. 2015

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Fibroblast activation protein-α promotes ovarian cancer cell proliferation and invasion via extracellular and intracellular signaling mechanisms

Cited by 39 publications

References 23 publications

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

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

<p>Fibroblast Activation Protein (FAP) Overexpression Induces Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma by Down-Regulating Dipeptidyl Peptidase 9 (DPP9)</p>

Fibroblast activation protein‐α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations

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