MCPIP1 Controls Hybrid EMT and Tumor Stemness via the IL6 / JAK2 / STAT3 Axis in Pancreatic Cancer

作者：Xihui Ding, Yingying Zheng, Min Liu, F. Anthony Lai, Shiqi Liu, Qiuping Chen, Zihao Zhu, Huanzhong Liu, Xiaohui Li, Jinyong Xu, Rui Wang, Zhenhua Ren · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.71179 · 被引用次数：3 · 研究领域：Cytokine Signaling Pathways and Interactions、Chemokine receptors and signaling、Cancer Cells and Metastasis

INTRODUCTION: Pancreatic cancer (PC) is a common malignant tumor with high morbidity and mortality and a very poor prognosis, highlighting the urgent need to identify molecular therapeutic targets. Monocyte chemotactic protein-inducible protein-1 (MCPIP1) is a common inflammatory protein associated with the pathogenesis of a variety of cancers, although a comprehensive understanding of its function and the underlying mechanisms involved in PC remains unclear. MATERIALS AND METHODS: Immunohistochemistry, western blotting, immunofluorescence, flow cytometry, Transwell, and the scratch assay were used to evaluate the functional role of MCPIP1 in PC. Human PC samples, PC cells, and tumor tissues from subcutaneous tumors of nude mice were examined for MCPIP1 and a panel of epithelial-mesenchymal transition (EMT) -related indicators. In the mechanistic study, the IL6/JAK/STAT3 signaling pathway was investigated as a potential downstream pathway. IL6 activity was inhibited using the pharmacological inhibitor LMT-28 and was applied to MCPIP1 gene-deficient cells to assess the reversal of the malignant phenotype. RESULTS: MCPIP1 was significantly downregulated in PC tissues and its expression strongly correlated with patient survival. MCPIP1 knockdown enhanced tumor cell stemness, proliferation, migration, and hybrid epithelial-mesenchymal transition (hybrid EMT) in PC cell lines, whereas overexpression suppressed these phenotypes. In xenograft models, MCPIP1 knockdown promoted tumor ...