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  • br Acknowledgement br Special thanks to Dr


    Special thanks to Dr. Austin Cape for his helpful editing advances.
    Ethics approval
    Not applicable.
    Competing interests
    The authors declare that they have no competing interests.
    Authors' contributions
    Ling Su and Xiangguo Liu conceived the project. Shun Yao, Xiangguo Liu, and Ling Su designed experiments and analyzed data and drafted the manuscript. Shun Yao, Feifei Shi and Wenbo Sun and Yifeng Zhang conducted the experiments. Xiaoyang Sun, Yingying Wang and Xianfang Liu contributed to animal experiments. All authors have read and approved the final manuscript.
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    ANGPTL6-mediated angiogenesis promotes alpha fetoprotein-producing gastric cancer progression 
    Erbao Chena,1, Cheng Tanga,1, Ke Penga, Xi Chenga, Yichou Weia, Tianshu Liua,b,
    a Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
    b Center of Evidence-based Medicine, Fudan University, Shanghai, China
    Alpha-fetoprotein producing-gastric cancer
    Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is regarded as a rare but highly malignant gastric adenocarcinoma subtype and its clinic pathological presentation mimics hepatocellular carcinoma. However, the underlying mechanism of this disease remains elusive. The level of ANGPTL6 in AFPGC cell lines is much higher than that of common types of gastric cancer cells. A high level of ANGPTL6 confers a poor prognosis and is correlated with the expression of CD34 (an endothelial cell marker). ANGPTL6 promotes endothelial cell mi-gration and tube formation, Moreover, ANGPTL6 knockdown inhibits cancer cell apoptosis and invasiveness. Mechanistically, ANGPTL6 activates the ERK1/2 and AKT pathways. Treatment of ERK1/2 or AKT inhibitor can attenuated cell migration and tube formation. ANGPTL6 loss results in tumor growth in vivo. Our study revealed that ANGPTL6 is an important driver gene of angiogenesis in AFPGC development. These findings provide not only an effective biomarker for diagnosis but also an attractive therapeutic target for use in AFPGC patients.