Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis

被引：271

作者：

Bu, Pengcheng ^{[1
,2
,3
]}

Chen, Kai-Yuan ^{[3
]}

Xiang, Kun ^{[3
]}

Johnson, Christelle ^{[4
,5
]}

Crown, Scott B. ^{[6
]}

Rakhilin, Nikolai ^{[3
,5
]}

Ai, Yiwei ^{[4
]}

Wang, Lihua ^{[3
]}

Xi, Rui ^{[3
]}

Astapova, Inna ^{[6
,7
]}

Han, Yan ^{[3
]}

Li, Jiahe ^{[4
]}

Barth, Bradley B. ^{[3
]}

Lu, Min ^{[8
]}

Gao, Ziyang ^{[3
]}

Mines, Robert ^{[3
]}

Zhang, Liwen ^{[1
,2
]}

Herman, Mark ^{[6
,7
]}

Hsu, David ^{[7
,8
]}

Zhang, Guo-Fang ^{[6
,7
]}

Shen, Xiling ^{[3
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA

[4] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA

[5] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA

[6] Duke Univ, Mol Physiol Inst, Durham, NC 27701 USA

[7] Duke Univ, Dept Med, Durham, NC 27701 USA

[8] Duke Univ, Duke Canc Inst, Div Med Oncol, Durham, NC 27710 USA

来源：

CELL METABOLISM | 2018年 / 27卷 / 06期

基金：

中国国家自然科学基金; 美国国家科学基金会;

关键词：

MASS ISOTOPOMER DISTRIBUTIONS; COLORECTAL-CANCER; DIETARY FRUCTOSE; EXPRESSION; GLUCOSE; CELLS; TUMOR; FLUOROURACIL; LEUCOVORIN; SIGNATURE;

D O I：

10.1016/j.cmet.2018.04.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth.

引用

页码：1249 / +

页数：18

共 67 条

[1]

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes [J].