SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter

Naren Gupta, Pamela M. Martin, Puttur D. Prasad, Vadivel Ganapathy

Research output: Contribution to journalReview article

129 Scopus citations

Abstract

The identification of SLC5A8 as a tumor suppressor gene in colorectal cancer marks, for the first time, the association of a plasma membrane transporter with tumor suppressive properties. The subsequent establishment of the functional identity of SLC5A8 as a Na+-coupled transporter for short-chain monocarboxylates provides a mechanism for the tumor suppressive function of the transporter. Butyrate, a substrate for the transporter, is a histone deacetylase inhibitor and protective against colorectal cancer. This fatty acid is produced in the colonic lumen by bacterial fermentation of dietary fiber. SLC5A8 mediates the concentrative entry of butyrate from the lumen into colonocytes. Consequently, the transport function of SLC5A8 has the ability to influence the acetylation status of histones and hence gene expression in colonocytes. The ability of SLC5A8 to deliver butyrate into colonic epithelial cells most likely underlies the tumor suppressive role of this transporter.

Original languageEnglish (US)
Pages (from-to)2419-2425
Number of pages7
JournalLife sciences
Volume78
Issue number21
DOIs
StatePublished - Apr 18 2006

Keywords

  • Butyrate
  • Colon cancer
  • Colonic bacteria
  • Dietary fiber
  • Histone deacetylases
  • SLC5A8
  • Short-chain fatty acids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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