Jiaping Tang

Southeast University, China

Title: Acetyl- CoA Carboxylase 1 Down regulation Promotes Esophageal Squamous Cell Carcinoma Metastasis by Activating the CXCL8–Neutrophil Extracellular Trap Axis

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Biography

Jiaping Tang is a second-year Ph.D. candidate at the School of Medicine, Southeast University, where she is mentored by Professor Jiahua Zhou. She obtained her Master of Medicine degree from Nankai University in 2019. Her research currently concentrates on two key areas: metastasis of esophageal cancer and perineural invasion in pancreatic cancer. Specifically, she investigates the molecular drivers of tumor spread and the mechanisms by which cancer cells interact with the nervous system to promote invasion and disease progression. Her work integrates in vitro models, animal studies, and clinical tissue analysis to identify potential prognostic biomarkers and novel therapeutic targets. Ms. Tang has presented her findings at national oncology meetings and has co-authored several research articles in international journals. She is an active member of the Chinese Anti-Cancer Association and is dedicated to translating basic research into clinical applications for improved patient outcomes.

Abstract

Esophageal squamous cell carcinoma (ESCC) metastasis remains a major cause of poor prognosis. Acetyl- CoA carboxylase 1 (ACC1), a rate- limiting enzyme in fatty acid synthesis, has been implicated in tumor progression but its role in ESCC is unclear. This study investigated whether and how ACC1 downregulation drives ESCC metastasis.

ACC1 expression was examined in 98 ESCC patient tissues by RT- qPCR and in a 91- sample tissue microarray by immunohistochemistry. ACC1 knockdown and overexpression were established in KYSE- 450, KYSE- 150 and KYSE- 140 cells. Cell migration and invasion were assessed by Transwell assays. RNA- seq, chromatin immunoprecipitation, and dual- luciferase reporter assays were used to identify downstream targets. Neutrophil recruitment and neutrophil

extracellular trap (NET) formation were evaluated in vitro using human peripheral blood neutrophils. A tail- vein lung metastasis model in BALB/c nude mice was used for in vivo validation, with or without the PAD4 inhibitor (NET inhibitor).

Low ACC1 expression correlated significantly with lymph node metastasis and shorter overall survival in ESCC patients. ACC1 knockdown did not alter fatty acid levels or proliferation but markedly enhanced ESCC cell migration and invasion. Mechanistically, ACC1 knockdown increased intracellular acetyl- CoA, leading to p300- dependent histone H3 acetylation, which upregulated c- Fos and consequently CXCL8 transcription. CXCL8 activated PI3K/AKT and

MEK/ERK signaling via CXCR1/2, induced epithelial- mesenchymal transition, and promoted autocrine migration/invasion. Paracrinally, CXCL8 recruited neutrophils and induced NET formation, further facilitating ESCC cell migration. In vivo, ACC1 knockdown increased lung metastasis, which was suppressed by PAD4 inhibitor treatment. Clinically, high CXCL8 levels and abundant NETs in ESCC tissues were associated with poor prognosis.

ACC1 downregulation promotes ESCC metastasis through a dual autocrine and paracrine mechanism involving the CXCL8–NET axis. Targeting this axis may offer a therapeutic strategy for ESCC patients with low ACC1 expression.

Keywords

Acetyl- CoA carboxylase 1, CXCL8, Esophageal squamous cell carcinoma, Neutrophil extracellular traps.