MORC2 Enhances Tumor Growth by Promoting Angiogenesis and Tumor-Associated Macrophage Recruitment via Wnt/β-Catenin in Lung Cancer

Cellular Physiology and Biochemistry

Meihan Liu¹ 

关键词: MORC2;    Growth;    TAM;    Lung cancer;    Stem-like cells;   

DOI  :  10.1159/000495673

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims In this study, we aimed to investigate how MORC family CW-type zinc finger 2 (MORC2) affects tumor progression of lung cancer. Methods The MORC2 level was analyzed by real-time RT-PCR and immunohistochemistry (IHC) in normal control tissues and lung cancers. LL/2 cells overexpressing MORC2 were used to study how MORC2 expression influences lung cancer progression. The effects of MORC2 on cell viability, migration and invasion were assessed by MTT assay, Western blotting, and transwell assays, respectively. Afterwards, the effects of MORC2 on the activation of the Wnt/β-catenin pathway were explored by Western blotting. The effects of MORC2 on tumor-associated macrophages (TAM) were determined by immunofluorescence (IF) staining, real-time RT-PCR and Western blotting. Results Our results showed that MORC2 was upregulated in lung cancers relative to adjacent tissues. The results also demonstrated that MORC2 promoted lung cancer tumor growth in vivo. Additionally, MORC2 overexpression stimulated the upregulation of vascular endothelial growth factor (VEGF), driving angiogenesis. MORC2 overexpression in LL/2 also increased the amount of aldehyde dehydrogenase-1 (ALDH1) protein, indicating that MORC2 increased cancer stem cell features. We further determined that MORC2 activated Wnt/β-catenin signaling in lung cancer cells. Upregulation of macrophage-recruiting genes including VEGF and Macrophage-specific colony stimulating factor (CSF-1) recruits TAMs to the tumor site, which has the net effect of promoting additional tumor growth and metastasis. Conclusion Our data suggest that MORC2 overexpression can drive lung cancer growth by stimulating the recruitment of TAMs in addition to angiogenesis and that activation of Wnt/β-signaling may be a key pathway underlying this phenotype that is amenable to pharmacological intervention.

【 授权许可】

CC BY-NC-ND