ACC1/CXCL8/NETs paper raw data

Esophageal squamous cell carcinoma (ESCC) presents a considerable challenge in terms of prognosis, primarily due to its highly metastatic nature, although the precise mechanisms driving metastasis remain elusive. Here, we investigate the role of the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 in ESCC metastasis, with a specific focus on its interaction with the chemokine CXCL8 and neutrophil extracellular traps (NETs). We demonstrate that ACC1 knockdown up-regulates CXCL8 expression, thereby driving ESCC cell migration and invasion through the activation of the PI3K/AKT and MEK/ERK signaling pathways in an autocrine manner. Additionally, ACC1 knockdown induces neutrophil recruitment and NET formation via a CXCL8-dependent paracrine mechanism, further facilitating ESCC metastasis. Mechanistically, ACC1 knockdown enhances histone acetylation, leading to the increased expression of the transcription factor c-Fos, which in turn promotes CXCL8 transcription. Clinically, we observe that low ACC1 expression and high CXCL8 levels are associated with poorer prognosis in ESCC patients, while elevated levels of NETs correlate with shorter overall survival. These findings highlight the significance of the ACC1-CXCL8-NET axis in driving ESCC progression, suggesting its potential as both a therapeutic target and a prognostic marker for ESCC management.