Chen Hongmei, Zhang Lei, He Wenting, Liu Tao, Zhao Yang, Chen Hao, Li Yumin
Institute of Cell Biology, School of Life Sciences, Lanzhou University, 222 Tian-Shui South Road, Lanzhou 730000, Gansu, China; Institute of Medical Physiology and Psychology, School of Basic Medical Sciences, Lanzhou University, 199 Dong-Gang West Road, Lanzhou 730000, Gansu, China.
Department of General Surgery, The First Hospital of Lanzhou University, 1 Dong-Gang West Road, Lanzhou 730000, Gansu, China.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):475-481. doi: 10.1016/j.bbrc.2018.01.048. Epub 2018 Jan 9.
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation. Significantly, co-immunoprecipitation (Co-IP) analyses indicated that ESCO2 can interact with p53 in GC cells. Taken together, our data demonstrate that ESCO2 is essential for the development of GC and might be a potential therapeutic target for treating GC.
黏连蛋白1同源物2(ESCO2)是调控黏连和基因组稳定性的必需基因,尚未在人类胃癌(GC)中进行研究。我们发现,在人胃癌细胞系中敲低ESCO2可显著抑制体外细胞增殖并诱导细胞凋亡,在体内可抑制肿瘤异种移植的发展。此外,腺苷单磷酸激活的蛋白激酶(AMPK)在其下游靶点包括雷帕霉素靶蛋白(mTOR)和p70核糖体S6激酶1(p70S6K1)受到抑制后被激活,这一结果与p53激活一致。重要的是,免疫共沉淀(Co-IP)分析表明,ESCO2可在胃癌细胞中与p53相互作用。综上所述,我们的数据表明ESCO2对胃癌的发展至关重要,可能是治疗胃癌的潜在治疗靶点。