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Oncogene:上海交大发表肿瘤代谢研究新成果

摘要 : 肿瘤代谢异常是肿瘤十大特征性标志之一,并成为近年来肿瘤基础研究的热点。近日,上海交通大学医学院附属仁济医院核医学科研究团队最新成果:该研究首次发现了p54nrb蛋白Y267突变体在抑制肿瘤脂质合成的同时遏制肿瘤细胞的生长和发生,揭示了p54nrb经SREBP1激活肿瘤细胞脂代谢和肿瘤发生的分子机制。

 肿瘤代谢异常是肿瘤十大特征性标志之一,并成为近年来肿瘤基础研究的热点。近日,国际学术权威杂志《Oncogene》(SCI IF=8.559)在线发表上海交通大学医学院附属仁济医院核医学科研究团队最新成果:p54/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A。该研究首次发现了p54nrb蛋白Y267突变体在抑制肿瘤脂质合成的同时遏制肿瘤细胞的生长和发生,揭示了p54nrb经SREBP1激活肿瘤细胞脂代谢和肿瘤发生的分子机制。这项研究成果是由核医学科2014届硕士研究生朱宗平和赵小平副研究员共同完成,黄钢教授和刘建军教授为通讯作者。

仁济医院核医学科研究团队在学科带头人黄钢教授带领下,近年来一直围绕肿瘤代谢PET/CT显像的分子机制开展基础研究,冀望以肿瘤代谢研究为突破,应用分子影像技术手段,结合分子生物学实验方法,揭示了肿瘤代谢异常的关键分子机制,为PET/CT代谢显像指导临床肿瘤个体化治疗提供科学依据。研究团队近5年科室承担包括973、国家自然基金重点项目等国家级课题11项,发表大于5分SCI收录论文13篇,荣获华夏医学科技一等奖、上海市科技进步奖等省部级奖项6项。此次研究成果在《Oncogene》杂志发表,表明该研究团队在肿瘤代谢方面研究已经得到国际认可。

原文标题:p54nrb/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A

原文摘要:Dysregulation of lipid metabolism is common in breast cancer. However, the underlying mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of breast cancer is poorly understood. Here, we show that the nuclear protein p54nrb/Nono is highly expressed in breast cancer tissues as compared with the adjacent normal tissues in human patients. To determine the functions of p54nrb in breast cancer, we performed a biochemical screen and identified SREBP-1a, a master activator for genes involved in lipid biosynthesis, as a novel interacting protein of p54nrb. In human breast cancer tissues, the levels of p54nrb and SREBP-1a proteins were positively correlated with each other. Our biochemical analyses showed that the conserved Y267 residue of p54nrb was required for its binding to the nuclear form of SREBP-1a. Interestingly, p54nrb binding to nuclear SREBP-1a caused an increase of nuclear SREBP-1a protein stability. As a result, p54nrb stimulates SREBP-1-meidated transcription of lipogenic genes and lipid production in breast cancer cells. Moreover, both p54nrb and SREBP-1a were required for breast cancer cell growth in vitro, and p54nrb binding to nuclear SREBP-1a was also critical for breast tumor development in vivo. Together, we conclude that p54nrb is a novel regulator of SREBP-1a in the nucleus, and our data suggest that p54nrb regulation of SREBP-1a supports the increased cellular demand of lipids for breast cancer growth. Thus, the SREBP pathway may represent a novel target for treating breast cancer.

来源: Oncogene 浏览次数:0

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