脂肪酸氧化驱动的Src将三阴性乳腺癌中的线粒体能量重编程与致癌特性联系起来。
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
作者信息
Park Jun Hyoung, Vithayathil Sajna, Kumar Santosh, Sung Pi-Lin, Dobrolecki Lacey Elizabeth, Putluri Vasanta, Bhat Vadiraja B, Bhowmik Salil Kumar, Gupta Vineet, Arora Kavisha, Wu Danli, Tsouko Efrosini, Zhang Yiqun, Maity Suman, Donti Taraka R, Graham Brett H, Frigo Daniel E, Coarfa Cristian, Yotnda Patricia, Putluri Nagireddy, Sreekumar Arun, Lewis Michael T, Creighton Chad J, Wong Lee-Jun C, Kaipparettu Benny Abraham
机构信息
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Institute of Clinical Medicine, National Yang-Ming University and Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
出版信息
Cell Rep. 2016 Mar 8;14(9):2154-2165. doi: 10.1016/j.celrep.2016.02.004. Epub 2016 Feb 25.
Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC). Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.
利用线粒体转移胞质杂种和多种组学方法来了解三阴性乳腺癌（TNBC）中的线粒体重编程和线粒体调节的癌症通路。对胞质杂种和已建立的乳腺癌（BC）细胞系的分析表明，转移性TNBC通过脂肪酸β氧化（FAO）维持高水平的ATP，并通过Y419位点的自磷酸化激活Src癌蛋白。对FAO的调控，包括敲低FAO的限速蛋白肉碱棕榈酰转移酶-1A（CPT1）和2（CPT2），以及对患者来源的异种移植模型的分析，证实了线粒体FAO在Src激活和转移中的作用。对癌症基因组图谱（TCGA）和其他独立的BC临床数据的分析进一步重申了线粒体FAO和CPT基因在Src调节中的作用及其在BC转移中的重要性。
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