Science再次证实:除了基因突变,肿瘤组织起源也很重要
2016/09/13
上周,发表在Science上的一篇论文中,来自MIT等机构的科学家们在小鼠中进行了癌症研究。他们的发现再次肯定了先前的研究结果——基因突变和肿瘤组织起源都影响着恶性肿瘤细胞的行为。


9月9日,Science杂志上发表了题为“Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers”论文。来自MIT等机构的科学家们在小鼠模型中进行了癌症研究。他们的发现再次肯定了先前的研究结果——基因突变和肿瘤组织起源都影响着恶性肿瘤细胞的行为。

胰腺或肺部Kras的激活和Trp53的缺失分别会引发胰腺导管腺癌(pancreatic ductal adenocarinoma ,PDAC)或非小细胞肺癌(NSCLC)。尽管引发癌症的起始事件(initiating events)相同,但这两种肿瘤利用支链氨基酸(branched-chain amino acids ,BCAAs)的方式并不同。


Metabolic differences in tumors of different origins.

NSCLC肿瘤会将自由的BCAAs合并到组织蛋白中,将BCAAs作为一种氮源。然而,PDAC肿瘤减少了BCAA的吸收。BCAA降解酶的表达水平反映了两者间的差异。Bcat1和Bcat2(利用BCAA所需的酶)的缺失影响了NSCLC肿瘤形成,但PDAC肿瘤形成并不需要这些酶。

研究揭示了肺肿瘤和胰腺肿瘤获取生存所需氮的不同方式,表明组织起源是癌症如何满足代谢需求的重要决定因素。

同日,Science杂志还针对这一研发发表了一篇题为“Location, location, location”的Perspective。作者们指出,在这项新研究中,科学家们证明,肿瘤首次出现的组织位置实际上与驱动突变的机制同样重要。文章指出,这一结果不仅为组织起源在肿瘤发展中发挥作用提供了更多的证据,也可能会引起与肿瘤生长早期区域相关标志物的发展。

备注:本文部分内容编译自medicalxpress,原标题“Study reaffirms the belief that malignant cell behavior is influenced by the tumor tissue of origin”。

所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
查看更多
  • Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers

    Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non–small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test