ASAP3 activates the NF-κB signaling pathway to promote the progression of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Despite advances in diagnosis and treatment, the lack of effective therapeutic targets continues to limit improvements in patient outcomes. ASAP3 has been implicated in tumor progression; however, its role and underlying mechanisms in ESCC remain unclear.

Paraffin-embedded ESCC tissues were analyzed by immunohistochemistry to evaluate the expression of ASAP3, NEMO, p65, phosphorylated p65 (p-p65), and MMP9 and their associations with clinicopathological parameters. In vitro, ASAP3 was silenced to assess its effects on ESCC cell proliferation, migration, and invasion and to explore the underlying mechanisms. In vivo, the role of ASAP3 in ESCC growth was validated using a mouse xenograft model, with tumor size and volume measured and changes in ASAP3, NEMO, p65, and p-p65 expression further analyzed.

Clinicopathological analysis showed that elevated ASAP3, NEMO, p65, p-p65, and MMP9 expression in ESCC tissues was associated with poor prognosis. In vitro, ASAP3 knockdown inhibited the proliferation, migration, and invasion of KYSE450 cells. In vivo, ASAP3 silencing suppressed xenograft tumor growth and reduced tumor proliferative activity. Mechanistically, ASAP3 downregulation decreased NEMO expression and p65 phosphorylation, thereby suppressing ESCC cell proliferation, migration, and invasion.

Collectively, ASAP3 may promote ESCC progression by interacting with NEMO and activating NF-κB signaling. These findings suggest that ASAP3 functions as an oncogenic driver and may serve as a potential biomarker in ESCC.