In vivo library screening identifies the metabolic enzyme aldolase A as a promoter of metastatic lung colonization.
In vivo library screening identifies the metabolic enzyme aldolase A as a promoter of metastatic lung colonization.
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体内文库筛选将代谢酶醛缩酶 A 鉴定为转移性肺定植的促进剂。
DOI：
10.1016/j.isci.2021.102425
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发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Karnoub AE
中科院分区：
文献类型：
--
作者：
Tu Z;Hou S;Zheng Y;Abuduli M;Onder T;Intlekofer AM;Karnoub AE
对促进播散性肿瘤细胞（dtc）向危及生命的病变生长的因素的阐明，将为转移性癌症患者提供急需的预后和治疗靶点。为了确定这些调节因子，我们进行了功能获得性cDNA文库筛选，以发现促进前列腺癌细胞在小鼠肺部定植的基因作为实验模型。我们的研究发现，代谢酶醛缩酶A （ALDOA）是癌细胞运动、非锚定生长和转移性定殖的驱动因素，也是许多恶性肿瘤（包括前列腺癌、乳腺癌、胰腺癌和肝癌）患者不良预后的预测因子。代谢组学结合生化和功能分析表明，ALDOA触发了腺苷-5 ' -单磷酸腺苷（AMP）活化蛋白激酶（AMPK）的激活，我们证明了AMPK在表达ALDOA的细胞中具有重要的促恶性活性。总的来说，这些发现揭示了体内方法来鉴定转移性定植调节因子，并揭示了先前未描述的ALDOA-AMPK通路在肿瘤进展中的作用。功能获得性cDNA筛选确定几个潜在的转移基因Aldolase A促进转移性肺定殖Aldolase A调节癌细胞中ampk依赖的恶性特征Aldolase A是癌症进展的预后生物标志物；癌症;代谢组学
Elucidations of the factors that promote the growth of disseminated tumor cells (DTCs) into life-threatening lesions stand to provide much needed prognostic and therapeutic targets of translational utility for patients with metastatic cancer. To identify such regulators, we conducted gain-of-function cDNA library screening to discover genes that foster prostate cancer cell colonization of mouse lungs as an experimental model. Our efforts identified the metabolic enzyme aldolase A (ALDOA) as a driver of cancer cell motility, anchorage-independent growth, and metastatic colonization, and as a prognosticator of adverse patient outcome across many malignancies, including prostate, breast, pancreatic, and liver cancers. Metabolomics coupled with biochemical and functional analyses revealed that ALDOA triggered the activation of adenosine-5′-monophosphate (AMP)-activated protein kinase (AMPK), which we demonstrate played essential promalignant activities in ALDOA-expressing cells. Collectively, these findings unveiled vivo approaches to identify metastatic colonization regulators and uncovered previously undescribed roles for ALDOA-AMPK pathway in tumor progression. Gain-of-function cDNA screen identifies several potential metastatic genes Aldolase A promotes metastatic lung colonization Aldolase A regulates AMPK-dependent malignancy traits in cancer cells Aldolase A is a prognostic biomarker of cancer progression Cancer Systems Biology; Cancer; Metabolomics
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影响因子：
7.5
作者：
Hämälistö S;Jäättelä M
通讯作者：
Jäättelä M
影响因子：
8
作者：
Martin, SS;Ridgeway, AG;Leder, P
通讯作者：
Leder, P
DOI：
10.1002/hed.23169
发表时间：
2013-10-01
影响因子：
2.9
作者：
Lessa, Roberta C.;Campos, Antonio Hugo J. F. M.;Vettore, Andre Luiz
通讯作者：
Vettore, Andre Luiz
DOI：
10.1007/978-3-030-32656-2_9
发表时间：
2019-01-01
期刊：
PROSTATE CANCER: CELLULAR AND GENETIC MECHANISMS OF DISEASE DEVELOPMENT AND PROGRESSION, 2ND EDITION
影响因子：
--
作者：
DiNatale, Anthony;Fatatis, Alessandro
通讯作者：
Fatatis, Alessandro
影响因子：
4.2
作者：
Long, Feng;Cai, Xinyan;Li, Kanghua
通讯作者：
Li, Kanghua