An LCN2-Dependent Positive-Feedback Loop Between Gastric Cancer Cells and Tumor-Associated-Macrophages Mediates Lymphangiogenesis and Lymphatic Metastasis.

ABSTRACT: Lymph node (LN) metastasis is a major determinant of poor prognosis in patients with gastric cancer (GC). Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor metastasis and progression; however, the underlying mechanisms through which TAMs induce LN metastasis in GC remain poorly understood. This study demonstrates that low lipocalin-2 (LCN2) expression is associated with increased LN metastasis and shorter survival in GC. Functionally, LCN2 silencing significantly increases M2-type TAM infiltration, lymphangiogenesis, and LN metastasis. Mechanistically, LCN2 downregulates the NF-κB pathway-mediated CCL5 expression by interacting with Annexin A1, which inhibits K63- and M1-linked ubiquitination of NEMO. Furthermore, LCN2-regulated CCL5 recruits and repolarizes TAMs t

SUBMITTER: Huang Z 

PROVIDER: S-EPMC12667518 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature