MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8 + T Cell Apoptosis via the Wnt/β‐Catenin Pathway
Year: 2025
Type: article
Abstract: ABSTRACT Enhanced macrophage M2 polarization and CD8 + T cell dysfunction contribute to the pathophysiology of non‐small cell lung cancer (NSCLC). Motor neuron and pancreatic homeobox 1 (MNX1) has emerged as a potential tumor‐promoting player. Here, we clarified the activity of MNX1 in NSCLC. PMA‐induced THP‐1 M0‐like macrophages or CD8 + T cells were co‐cultured with NSCLC cells. Cell colony formation, migration, proliferation, apoptosis, and invasiveness were assessed by colony formation, wound healing, CCK‐8, flow cytometry, and transwell assays, respectively. The ratio of CD206 + macrophages was analyzed by flow cytometry. Ki‐67 expression was tested by immunofluorescence. ChIP and luciferase assays were used to evaluate the relationship between MYCN and MNX1. MNX1 was highly expressed in NSCLC, and its loss‐of‐function suppressed cell growth, motility, and invasiveness in NSCLC cells. MNX1 depletion also diminished macrophage M2 polarization and CD8 + T cell apoptosis. Mechanistically, MYCN increased MNX1 expression at the transcriptional level. MNX1 increase reversed the impact of MYCN depletion on NSCLC cell malignant behaviors, macrophage M2 polarization, and CD8 + T cell viability. MYCN depletion diminished the in vivo growth of A549 subcutaneous xenografts. Additionally, MNX1 increase counteracted the impact of MYCN depletion on the Wnt/β‐catenin pathway. Our findings elucidate the oncogenic role of the MYCN/MNX1/Wnt/β‐catenin pathway in NSCLC by driving macrophage M2 polarization and diminishing CD8 + T cell viability. Our study thus uncovers a novel mechanism underlying NSCLC development and highlights potential targets for combating NSCLC.
DOI: 10.1002/jbt.70251
Authors: Chengzhang Cao, Haiyin Lai, Yuzhen Shi
Institution: Fujian Medical University
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4409433662