CEACAM7 enhances oral cancer metastasis by upregulating CD317 expression

Aims: Carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) is involved in the regulation of normal cell differentiation. Although numerous studies have demonstrated a strong association between CEACAM7 expression and cancer progression, its specific role in the development and metastasis of oral cancer remains largely uncharacterized. Materials and methods: Using RNA sequencing technology, transwell migration/invasion assays, western blotting, luciferase reporter, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and a xenograft model, the effects of CEACAM7 on cell migration in human oral cancer cells were investigated. Key findings: In this study, analysis of the Gene Expression Omnibus (GEO) database revealed that patients with advanced-stage oral cancer or lymph node metastasis exhibited significantly elevated CEACAM7 expression, which correlated with poorer overall survival. RNA sequencing data further indicated that CEACAM7 overexpression upregulated the expression of CD317. Functional assays showed that CD317 overexpression enhanced the migratory capacity of oral cancer cells, whereas CD317 knockdown suppressed it. Pharmacological inhibition using JNK-IN-8 and PP1 suggested that CEACAM7 may regulate CD317 expression and cell migration via the phosphorylated JNK (p-JNK) and Src (p-Src) signaling pathways. The critical roles of CEACAM7 and CD317 in oral cancer metastasis were further validated using CEACAM7-stable cell lines, in vivo animal experiments, and clinical tissue specimens. Significance: These findings suggest that CEACAM7 promotes oral cancer metastasis by regulating CD317 through the p-JNK and p-Src pathways. CEACAM7 and CD317 may therefore represent potential therapeutic targets for the treatment of metastatic oral cancer.