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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bu, P; Chen, K-Y; Xiang, K; Johnson, C; Crown, SB; Rakhilin, N; Ai, Y; Wang, L; Xi, R; Astapova, I; Han, Y; Li, J; Barth, BB; Lu, M; Gao, Z; Mines, R; Zhang, L; Herman, M; Hsu, D; Zhang, G-F; Shen, X

Published Date

  • June 5, 2018

Published In

Volume / Issue

  • 27 / 6

Start / End Page

  • 1249 - 1262.e4

PubMed ID

  • 29706565

Pubmed Central ID

  • PMC5990465

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2018.04.003


  • eng

Conference Location

  • United States