Elevated ERβ expression driven by low ASB8-mediated ubiquitination in lung adenocarcinoma promotes lymph node metastasis via tumor-associated neutrophils.

ABSTRACT: This study investigated the role of estrogen receptor beta (ERβ) in the lymph node metastasis of lung adenocarcinoma (LUAD), focusing on its interaction with tumor-associated neutrophils (TANs) and its regulation of lymphangiogenesis. Clinical analysis of LUAD patient samples revealed that high ERβ expression was correlated with positive lymph node metastasis and increased lymphatic vessel density. In vitro experiments showed that ERβ promotes neutrophil chemotaxis by regulating CCL15 transcription, whereas TANs secrete VEGF-C, enhancing lymphangiogenesis. Using an orthotopic lung cancer model, we confirmed that ERβ facilitates LUAD lymph node metastasis through TAN recruitment, and inhibiting neutrophils with anti-Ly6G antibodies or CCR1 antagonists reduced this effect. Additionally, the

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12311189 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature