Regulation of the metabolite profile by an APC gene mutation in colorectal cancer

Tomoo Yoshie, Shin Nishiumi, Yoshihiro Izumi, Aya Sakai, Jun Inoue, Takeshi Azuma, Masaru Yoshida

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Mutation of the APC gene occurs during the early stages of colorectal cancer development. To obtain new insights into the mechanisms underlying the aberrant activation of the Wnt pathway that accompanies APC mutation, we carried out a gas chromatography-mass spectrometry-based semiquantitative metabolome analysis. In vitro experiments comparing SW480 cells expressing normal APC and truncated APC indicated that the levels of metabolites involved in the latter stages of the intracellular tricarboxylic acid cycle, including succinic acid, fumaric acid, and malic acid, were significantly higher in the SW480 cells expressing the truncated APC. In an in vivo study, we found that the levels of most amino acids were higher in the non-polyp tissues of APC min/+ mice than in the normal tissues of the control mice and the polyp tissues of APC min/+ mice. Ribitol, the levels of which were decreased in the polyp lesions of the APC min/+ mice and the SW480 cells expressing the truncated APC, reduced the growth of SW480 cells with the APC mutation, but did not affect the growth of SW480 transfectants expressing full-length APC. The level of sarcosine was found to be significantly higher in the polyp tissues of APC min/+ mice than in their non-polyp tissues and the normal tissues of the control mice, and the treatment of SW480 cells with 50 μM sarcosine resulted in a significant increase in their growth rate. These findings suggest that APC mutation causes changes in energetic metabolite pathways and that these alterations might be involved in the development of colorectal cancer.

Original languageEnglish
Pages (from-to)1010-1021
Number of pages12
JournalCancer Science
Volume103
Issue number6
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

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APC Genes
Colorectal Neoplasms
Mutation
Polyps
Sarcosine
Growth
Ribitol
Wnt Signaling Pathway
Citric Acid Cycle
Metabolome
Succinic Acid
Gas Chromatography-Mass Spectrometry
Amino Acids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yoshie, T., Nishiumi, S., Izumi, Y., Sakai, A., Inoue, J., Azuma, T., & Yoshida, M. (2012). Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. Cancer Science, 103(6), 1010-1021. https://doi.org/10.1111/j.1349-7006.2012.02262.x

Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. / Yoshie, Tomoo; Nishiumi, Shin; Izumi, Yoshihiro; Sakai, Aya; Inoue, Jun; Azuma, Takeshi; Yoshida, Masaru.

In: Cancer Science, Vol. 103, No. 6, 01.06.2012, p. 1010-1021.

Research output: Contribution to journalArticle

Yoshie, T, Nishiumi, S, Izumi, Y, Sakai, A, Inoue, J, Azuma, T & Yoshida, M 2012, 'Regulation of the metabolite profile by an APC gene mutation in colorectal cancer', Cancer Science, vol. 103, no. 6, pp. 1010-1021. https://doi.org/10.1111/j.1349-7006.2012.02262.x
Yoshie, Tomoo ; Nishiumi, Shin ; Izumi, Yoshihiro ; Sakai, Aya ; Inoue, Jun ; Azuma, Takeshi ; Yoshida, Masaru. / Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. In: Cancer Science. 2012 ; Vol. 103, No. 6. pp. 1010-1021.
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