KPNA2/KPNB1 promotes the malignant progression of gastric cancer induced by M2 macrophage polarization

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-12-31 DOI:10.1016/j.tice.2024.102714

Juan Bai , Ping Chen , Qingxia Zhou , Xiaojun Tie , Xiao Xia , Yan Wang , Ling Jin

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引用次数: 0

Abstract

Macrophages in the tumor microenvironment (TME) regulated gastric cancer progression, but the mechanism of macrophage polarization in gastric cancer progression remained unclear. This study mainly explored the molecular mechanism of macrophage polarization in the tumor microenvironment and its impact on the progression of gastric cancer. KPNA2 and KPNB1 expressions in cancer tissues and adjacent non-cancerous tissues were quantified via RT-qPCR and western blot. A correlation analysis was conducted between KPNA2 and KPNB1 expressions, utilizing the GEPIA2 database to link them with macrophage polarization. KPNA2-KPNB1 interaction was investigated on STRING, verified by Co-IP and IF assays. Raw246.7 cells were transfected with KPNA2 overexpression with or without si-KPNB1 plasmids. Then, M1/M2 macrophage markers and the proportion of M2 macrophages were measured by RT-qPCR, western blot, and IF. Co-culturing transfected Raw246.7 with MFC cells showed gastric cancer cell proliferation, apoptosis, migration, and invasion via CCK-8, flow cytometry, and transwell assays. KPNA2 and KPNB1 in gastric cancer tissues were elevated, exhibiting a positive correlation between them. KPNA2 overexpression facilitated the differentiation of macrophages into M2 type. KPNA2 overexpression in macrophages co-cultured with MFC cells stimulated MFC cells proliferation, repressed apoptosis, and enhanced migration/invasion. The interaction between KPNA2 and KPNB1 was confirmed through Co-IP and IF assays. Si-KPNB1 reversed the effects of KPNA2 overexpression on macrophages and gastric cancer cells. KPNA2 promoted the M2 polarization of macrophages by upregulating KPNB1, thereby inducing the proliferation and metastasis of gastric cancer.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.