SLC transporters as a novel class of tumour suppressors: Identity, function and molecular mechanisms

Yangzom D. Bhutia, Ellappan Babu, Sabarish Ramachandran, Shengping Yang, Muthusamy Thangaraju, Vadivel Ganapathy

Research output: Contribution to journalReview article

40 Scopus citations

Abstract

The role of plasma membrane transporters in cancer is receiving increasing attention in recent years. Several transporters for essential nutrients are up-regulated in cancer and serve as tumour promoters. Transporters could also function as tumour suppressors. To date, four transporters belonging to the SLC gene family have been identified as tumour suppressors. SLC5A8 is a Na+ -coupled transporter for monocarboxylates. Among its substrates are the bacterial fermentation products butyrate and propionate and the ubiquitous metabolite pyruvate. The tumoursuppressive function of this transporter relates to the ability of butyrate, propionate and pyruvate to inhibit histone deacetylases (HDAC). SLC5A8 functions as a tumour suppressor in most tissues studied thus far, and provides a molecular link to Warburg effect, a characteristic feature in most cancers. It also links colonic bacteria and dietary fibre to the host. SLC26A3 as a tumour suppressor is restricted to colon; it is a Cl- /HCO-3 exchanger, facilitating the efflux of HCO-3 . The likely mechanism for the tumour-suppressive function of SLC26A3 is related to intracellular pH regulation. SLC39A1 is a Z2+ transporter and its role in tumour suppression has been shown in prostate. Zn2+ is present at high concentrations in normal prostate where it elicits its tumour-suppressive function. SLC22A18 is possibly an organic cation transporter, but the identity of its physiological substrates is unknown. As such, there is no information on molecular pathways responsible for the tumour-suppressive function of this transporter. It is likely that additional SLC transporters will be discovered as tumour suppressors in the future.

Original languageEnglish (US)
Pages (from-to)1113-1124
Number of pages12
JournalBiochemical Journal
Volume473
Issue number9
DOIs
StatePublished - May 1 2016

Keywords

  • Citrate metabolism
  • Histone deacetylases (hdac) inhibition
  • Ph regulation
  • Slc transporters
  • Tumour suppressors.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'SLC transporters as a novel class of tumour suppressors: Identity, function and molecular mechanisms'. Together they form a unique fingerprint.

  • Cite this