Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions.
Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions.
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DOI：
10.1038/ncomms16031
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发表时间：
2017-07-07
影响因子：
16.6
通讯作者：
Vasseur S
中科院分区：
文献类型：
--
作者：
Olivares O;Mayers JR;Gouirand V;Torrence ME;Gicquel T;Borge L;Lac S;Roques J;Lavaut MN;Berthezène P;Rubis M;Secq V;Garcia S;Moutardier V;Lombardo D;Iovanna JL;Tomasini R;Guillaumond F;Vander Heiden MG;Vasseur S
组织结构有助于胰腺导管腺癌（PDAC）表型。PDAC内的癌细胞形成腺样结构，嵌入在营养和氧气稀缺的富含胶原蛋白的网状结构中。肿瘤细胞在这种环境中生存需要改变代谢，但允许PDAC细胞耐受这些条件的代谢修饰尚不完全清楚。在这里，我们证明，胶原蛋白作为脯氨酸水库PDAC细胞作为营养源时，其他燃料是有限的。我们发现PDAC细胞能够吸收胶原片段，这可以促进PDAC细胞在营养有限的条件下存活，并且胶原衍生的脯氨酸有助于PDAC细胞代谢。最后，我们表明，脯氨酸氧化酶（PRODH1）是所需的PDAC细胞增殖在体外和体内。总的来说，我们的研究结果表明，PDAC细胞外基质代表了肿瘤细胞的营养库，突出了这种癌症的代谢灵活性。癌细胞适应它们的新陈代谢以在有限的营养可用性中生存。在这里，作者表明，在葡萄糖或谷氨酰胺可用性有限的条件下，胰腺导管腺癌细胞可以使用胶原衍生的脯氨酸来促进TCA循环，并允许细胞在体外和体内存活。
Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer. Cancer cells adapt their metabolism to survive limited nutrient availability. Here, the authors show that in conditions of limited glucose or glutamine availability, pancreatic ductal adenocarcinoma cells can use collagen-derived proline to foster the TCA cycle and allow cell survival both in vitro and in vivo.
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影响因子：
11.2
作者：
Liu W;Glunde K;Bhujwalla ZM;Raman V;Sharma A;Phang JM
通讯作者：
Phang JM
影响因子：
3.7
作者：
Ikenaga N;Ohuchida K;Mizumoto K;Akagawa S;Fujiwara K;Eguchi D;Kozono S;Ohtsuka T;Takahata S;Tanaka M
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Tanaka M
影响因子：
64.8
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Jiang L;Shestov AA;Swain P;Yang C;Parker SJ;Wang QA;Terada LS;Adams ND;McCabe MT;Pietrak B;Schmidt S;Metallo CM;Dranka BP;Schwartz B;DeBerardinis RJ
通讯作者：
DeBerardinis RJ
影响因子：
8.4
作者：
Antoniewicz, Maciek R.;Kraynie, David F.;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
影响因子：
15.9
作者：
Leca, Julie;Martinez, Sebastien;Tomasini, Richard
通讯作者：
Tomasini, Richard