Abstract 629: Characterization of the molecular mechanism of APOC1 in anti-ferroptosis and lymph node microenvironment remodeling in ESCC metastasis process

Abstract

Abstract The invasion and metastasis affect the survival and prognosis of patients with esophageal carcinoma (ESCC). Through single-cell sequencing analysis of para-cancerous tissue, tumor tissue, normal lymph node tissue and lymph node metastasis tissue in 4 untreated ESCC patients, we found that APOC1 was specifically up-regulated in lymph node metastasis tissue and tumor tissue. In vitro and in vivo experiments revealed that APOC1 overexpression significantly promoted the migration and anti-ferroptosis function in ESCC. Also, APOC1 upregulation promotes M2 macrophage differentiation, Treg aggregation, and CD8 T cell immune inactivation in lymph node metastasis tissue. Mechanistically, APOC1 competes with NRF2 to bind Keap1, promoting nuclear translocation of NRF2 thus upregulating activation of the NRF2 pathway in tumor cells. For the lymph node metastasis tumor microenvironment, secreted APOC1 could upregulate the oxLDL which induced M2 macrophage polarization via CD36/JAK2/STAT3 axis. Overall, in this study, we explored the role and molecular mechanism of APOC1 in ESCC metastasis process which could provide a new molecular therapeutic approach to ESCC patients. Citation Format: Beilei Liu, Baifeng Zhang, Hongyu Zhou, Licheng Tan, Xiaona Fang, Lanqi Gong, Jie Luo, Jinlin Huang, Jiao Huang, Yuma Yang, Xinyuan Guan. Characterization of the molecular mechanism of APOC1 in anti-ferroptosis and lymph node microenvironment remodeling in ESCC metastasis process [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 629.