IADR Abstract Archives
FN14 Promotes Oral Keratinocyte Migration and Invasion
Objectives: Oral squamous cell carcinoma (OSCC) is a devastating disease with high mortality and profound social impact due to facial deformities and functional loss. Often preceded by oral potentially malignant disorders (OPMDs), OSCC progression remains challenging to predict due to poorly understood mechanisms. Spatial transcriptomics of OSCC tissue have revealed increased cell motility and matrix degradation pathways, as well as elevated expression of fibroblast growth factor-inducible 14 (Fn14) at the invasive front. Fn14 is a cytokine receptor activated by TNF-like weak inducer of apoptosis (TWEAK), initiating pro-inflammatory and invasion-related signaling pathways. This study investigates Fn14’s role in OSCC invasion, hypothesizing that its activation promotes cell migration and invadopodia formation, facilitating increased tumor invasion. The objective of this study is to determine the role of Fn14 activation in OSCC invasion through analysis of matrix degradation, cell motility, and related signaling pathways.
Methods: Two cell lines, UM-SCC1 and MOC2, were used to assess Fn14 activation's effects. Matrix degradation was measured using a fluorescent gelatin assay following TWEAK stimulation and Fn14 antagonism. Cell motility was analyzed via a scratch assay, while CDC42 activation and NF-κB phosphorylation were quantified using ELISA and western blotting, respectively.
Results: TWEAK stimulation led to a 12-fold increase in matrix degradation in SCC1 (P < 0.001) and an 8-fold increase in MOC2 (P = 0.001). Scratch assays showed a modest but significant 12% increase in SCC1 migration (P = 0.0047). Mechanistically, TWEAK activation enhanced CDC42 activity and NF-κB phosphorylation, supporting dual pathways for invasion—cytoskeletal remodeling and transcription-dependent signaling.
Conclusions: TWEAK stimulation promotes invadopodia formation and matrix degradation, highlighting its critical role in OSCC invasion. Targeting the Fn14-TWEAK axis could provide new insights into reducing OSCC invasiveness and improving our understanding of malignant transformation pathways.
Methods: Two cell lines, UM-SCC1 and MOC2, were used to assess Fn14 activation's effects. Matrix degradation was measured using a fluorescent gelatin assay following TWEAK stimulation and Fn14 antagonism. Cell motility was analyzed via a scratch assay, while CDC42 activation and NF-κB phosphorylation were quantified using ELISA and western blotting, respectively.
Results: TWEAK stimulation led to a 12-fold increase in matrix degradation in SCC1 (P < 0.001) and an 8-fold increase in MOC2 (P = 0.001). Scratch assays showed a modest but significant 12% increase in SCC1 migration (P = 0.0047). Mechanistically, TWEAK activation enhanced CDC42 activity and NF-κB phosphorylation, supporting dual pathways for invasion—cytoskeletal remodeling and transcription-dependent signaling.
Conclusions: TWEAK stimulation promotes invadopodia formation and matrix degradation, highlighting its critical role in OSCC invasion. Targeting the Fn14-TWEAK axis could provide new insights into reducing OSCC invasiveness and improving our understanding of malignant transformation pathways.