Abstract
Oral cancer is the sixth leading cause of cancer-related mortality in Taiwan, with over 90% of cases being oral cavity squamous cell carcinomas (OSCCs). The high mortality rate of OSCC is largely attributed to metastasis and locoregional relapse, underscoring the need to identify key drivers of tumor progression. To uncover proteins involved in OSCC relapse, we conducted an iTRAQ-based proteomic profiling of OSCC tissues from 6 patients with primary tumors and 4 patients with relapsed tumors. Lymphocyte cytosolic protein 1 (LCP1) emerged as a candidate associated with OSCC progression, further supported by transcriptomic analysis from The Cancer Genome Atlas (TCGA). LCP1 showed a 2.4-fold upregulation in relapsed tumors and correlated with poor patient survival. Functional assays revealed that LCP1 expression promoted tumor growth in vivo and enhances proliferation, migration, invasion, and cisplatin resistance in vitro across four OSCC cell lines. Mechanistically, LCP1 expression and phosphorylation were induced by EGF via the EGFR/PI3K/AKT and EGFR/ERK signaling pathways. Additionally, LCP1 activated the JAK2/STAT3 axis to upregulate pro-interleukin-1β (IL-1β) expression and IL-1β secretion, thereby amplifying OSCC cell aggressiveness. In summary, this study provides novel insights into the oncogenic role of LCP1 in OSCC, linking EGFR-mediated signals and IL-1β production, and identifies LCP1 as a promising target for therapeutic intervention.