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Review
. 2016 May 1;473(9):1113-24.
doi: 10.1042/BJ20150751.

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

Yangzom D Bhutia  1 , Ellappan Babu  1 , Sabarish Ramachandran  1 , Shengping Yang  1 , Muthusamy Thangaraju  2 , Vadivel Ganapathy  3
Affiliations
Review

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

Yangzom D Bhutia et al. Biochem J. .

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 tumour-suppressive 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 Zn(2+) transporter and its role in tumour suppression has been shown in prostate. Zn(2+) 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.

Keywords: SLC transporters; citrate metabolism; histone deacetylases (HDAC) inhibition; pH regulation; tumour suppressors.

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Figures

Figure 1
Figure 1. Role of SLC5A8 in colonic epithelium
(A) Normal colonic epithelium, (B) pre-malignant colonic cell and (C) malignant colonic cell.
Figure 2
Figure 2
Relationship of SLC5A8 to the entry of SCFA into colonic epithelial cells under high-fibre and low-fibre dietary conditions
Figure 3
Figure 3. Role of SLC26A3 in colonic epithelium
(A) Normal colonic epithelium and (B) malignant colonic cell.
See this image and copyright information in PMC

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