DataSheet_6_GJB3 promotes pancreatic cancer liver metastasis by enhancing the polarization and survival of neutrophil.xlsx

Connexins are membrane expressed proteins, which could assemble into hexamers to transfer metabolites and secondary messengers. However, its roles in pancreatic cancer metastasis remains unknown. In this study, by comparing the gene expression patterns in primary pancreatic cancer patients primary and liver metastasis specimens, we found that Gap Junction Protein Beta 3 (GJB3) significantly increased in Pancreatic ductal adenocarcinoma (PDAC) liver metastasis. Animal experiments verified that GJB3 depletion suppressed the hepatic metastasis of PDAC cancer cells. Further, GJB3 over expression increased the neutrophil infiltration. Mechanistic study revealed that GJB3 form channels between PDAC tumor cells and accumulated neutrophil, which transfer cyclic adenosine monophosphate (cAMP) from cancer to neutrophil cells, which supports the survival and polarization. Taken together, our data suggesting that GJB3 could act as a potential therapeutic target of PDAC liver metastasis.

连接蛋白（Connexins）是一类膜表达蛋白，可组装为六聚体以转运代谢物与第二信使。然而其在胰腺癌转移中的作用仍未明确。本研究通过对比原发性胰腺癌患者原发灶与肝转移标本的基因表达谱，发现间隙连接蛋白β3（GJB3）在胰腺导管腺癌（PDAC）肝转移组织中显著上调。动物实验验证，敲低GJB3可抑制PDAC细胞的肝转移能力。进一步研究显示，GJB3过表达会促进中性粒细胞浸润。机制研究揭示，GJB3可在PDAC肿瘤细胞与募集的中性粒细胞之间形成通道，将环磷酸腺苷（cAMP）从肿瘤细胞转运至中性粒细胞，从而支持中性粒细胞的存活与极化。综上，本研究数据表明GJB3可作为PDAC肝转移的潜在治疗靶点。