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二磷酸酶2通过限制线粒体生成抑制肉瘤进展

时间:2019-11-23 03:20 来源:www.86bts.com 作者:传奇私服

本期文章:《细胞—代谢》:Online/在线发表

果糖-1,6-二磷酸酶2(FBP2)通过抑制线粒体生成抑制肉瘤的进展,这一成果由美国宾夕法尼亚大学M. Celeste Simon团队近日取得。相关论文于2019年11月21日在线发表于国际学术期刊《细胞—代谢》。

软组织肉瘤(STS)的显著细胞和遗传异质性限制了靶向疗法的临床获益。研究人员发现,糖异生同工酶FBP2的表达在广泛的肉瘤亚型中被沉默,揭示了不同STS共有的明显的共同代谢特征。强制的FBP2表达通过两种不同的机制抑制肉瘤细胞和肿瘤的生长。

首先,胞质FBP2拮抗与“ Warburg效应”相关的糖酵解,从而抑制肉瘤细胞增殖。第二,核定位的FBP2通过抑制核呼吸因子和线粒体转录因子A(TFAM)的表达,以催化活性独立的方式抑制线粒体的生物发生和呼吸。

具体而言,核FBP2与c-Myc转录因子在TFAM位点共定位,并抑制c-Myc依赖性TFAM表达。FBP2的这一独特双重功能为其在STS中的选择性抑制提供了理论依据,从而确定了该恶性肿瘤的潜在代谢脆弱性和可能的治疗靶标。

附:英文原文

Title: Fructose-1,6-Bisphosphatase 2 Inhibits Sarcoma Progression by Restraining Mitochondrial Biogenesis

Author: Peiwei Huangyang, Fuming Li, Pearl Lee, Itzhak Nissim, Aalim M. Weljie, Anthony Mancuso, Bo Li, Brian Keith, Sam S. Yoon, M. Celeste Simon

Issue&Volume: November 21, 2019

Abstract: The remarkable cellular and genetic heterogeneity of soft tissue sarcomas (STSs) limitsthe clinical benefit of targeted therapies. Here, we show that expression of the gluconeogenicisozyme fructose-1,6-bisphosphatase 2 (FBP2) is silenced in a broad spectrum of sarcomasubtypes, revealing an apparent common metabolic feature shared by diverse STSs. EnforcedFBP2 expression inhibits sarcoma cell and tumor growth through two distinct mechanisms.First, cytosolic FBP2 antagonizes elevated glycolysis associated with the “Warburgeffect,” thereby inhibiting sarcoma cell proliferation. Second, nuclear-localizedFBP2 restrains mitochondrial biogenesis and respiration in a catalytic-activity-independentmanner by inhibiting the expression of nuclear respiratory factor and mitochondrialtranscription factor A (TFAM). Specifically, nuclear FBP2 colocalizes with the c-Myctranscription factor at the TFAM locus and represses c-Myc-dependent TFAM expression. This unique dual function of FBP2 provides a rationale for its selectivesuppression in STSs, identifying a potential metabolic vulnerability of this malignancyand possible therapeutic target.

DOI: 10.1016/j.cmet.2019.10.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30568-6

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx

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