Fibromodulin FMOD promotes oral squamous cell carcinoma via activating EGFR signaling axis
As a Class II small leucine-rich proteoglycan, fibromodulin (FMOD) plays critical roles in collagen fibrillogenesis and angiogenesis. However, the biological function of FMOD in oral squamous cell carcinoma remains unknown to date. In this study, immunohistochemistry and immunofluorescence assays identified that FMOD protein was located in cytoplasm and nucleus and was overexpressed in OSCC tissues and cell lines. Clinical analysis confirmed that FMOD overexpression showed a significant association with malignant progression (P=0.011) and lymph node metastasis (P=0.032) in OSCC patients. Moreover, loss-of-function studies verified that knockdown of FMOD significantly inhibited OSCC growth and metastasis in vitro and in vivo. Mechanismly, RNA sequencing studies further confirmed that. Knockdown of FMOD expression inhibited OSCC cell proliferation, migration, invasion, and tumor growth probably through altering transcriptome leading to active cell cycle, down-regulating Cell adhesion molecules and ECM-receptor interaction and through inhibiting EGFR-ERK and EGFR-AKT pathways. Overall design: To reveal the differentially expressed genes caused by FMOD depletion, we knocked down FMOD expression using 3 different shRNAs in OSCC cells. The transcriptome sequencing studies were performed by deep sequencing, using Illumina HiSeq 4000.