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Cell Metab. 2018 Jun 5;27(6):1249-1262.e4. doi: 10.1016/j.cmet.2018.04.003. Epub 2018 Apr 26.

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

Author information

1
Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. Electronic address: bupc@ibp.ac.cn.
2
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853, USA.
4
Molecular Physiology Institute, Duke University, Durham, NC 27701, USA.
5
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853, USA.
6
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
7
Molecular Physiology Institute, Duke University, Durham, NC 27701, USA; Department of Medicine, Duke University, Durham, NC 27701, USA.
8
Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC 27710, USA.
9
Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
10
Department of Medicine, Duke University, Durham, NC 27701, USA; Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC 27710, USA.
11
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. Electronic address: xs37@duke.edu.

Abstract

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.

KEYWORDS:

ALDOB; Aldolase B; GATA6; colon cancer; colorectal cancer; fructose; liver; metabolic reprogramming; metabolism; metastasis

PMID:
29706565
PMCID:
PMC5990465
[Available on 2019-06-05]
DOI:
10.1016/j.cmet.2018.04.003

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