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

TitleAldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.
Publication TypeJournal Article
Year of Publication2018
AuthorsBu, P, K-Y Chen, K Xiang, C Johnson, SB Crown, N Rakhilin, Y Ai, L Wang, R Xi, I Astapova, Y Han, J Li, BB Barth, M Lu, Z Gao, R Mines, L Zhang, M Herman, D Hsu, G-F Zhang, and X Shen
JournalCell Metab
Volume27
Issue6
Start Page1249
Pagination1249 - 1262.e4
Date Published06/2018
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.

DOI10.1016/j.cmet.2018.04.003
Short TitleCell Metab