Na+/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: Molecular characterization of SMCT

Viktoriya Paroder, Shelly R. Spencer, Monika Paroder, Diego Arango, Simo Schwartz, John M. Mariadason, Leonard H. Augenlicht, Sepehr Eskandari, Nancy Carrasco

Research output: Contribution to journalArticle

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Abstract

We report an extensive characterization of the Na+/ monocarboxylate transporter (SMCT), a plasma membrane protein that mediates active transport of monocarboxylates such as propionate and nicotinate, and we show that SMCT may play a role in colorectal cancer diagnosis. SMCT, the product of the SLC5A8 gene, is 70% similar to the Na+/I- symporter, the protein that mediates active I- uptake in the basolateral surface of thyrocytes and other cells. SMCT was reported in the apical surface of thyrocytes and formerly proposed also to transport I - and was called the apical I- trans-porter. However, it is now clear that SMCT does not transport I-. Here we demonstrate a high-affinity Na+-dependent monocarboxylate transport system in thyroid cells, which is likely to be SMCT. We show that, whereas thyroidal Na+/I- symporter expression is thyroid-stimulating hormone (TSH)-dependent and basolateral, SMCT expression is TSH-independent and apical not only in the thyroid but also in kidney and colon epithelial cells and in polarized Madin-Darby canine kidney cells. We determine the kinetic parameters of SMCT activity and show its inhibition by ibuprofen (Ki = 73 ± 9 μM) in Xenopus laevis oocytes. SMCT was proposed to be a tumor suppressor in colon cancer [Li, H., et al. (2003) Proc. Natl. Acad. Sci. USA 100, 8412-8417]. Significantly, we show that higher expression of SMCT in colon samples from 113 colorectal cancer patients correlates with longer disease-free survival, suggesting that SMCT expression may be a favorable indicator of colorectal cancer prognosis.

Original languageEnglish (US)
Pages (from-to)7270-7275
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number19
DOIs
StatePublished - May 9 2006

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Colonic Neoplasms
Symporters
Colorectal Neoplasms
Carrier Proteins
Thyrotropin
Thyroid Gland
Colon
Madin Darby Canine Kidney Cells
Active Biological Transport
Niacin
Ibuprofen
Propionates
Xenopus laevis
Disease-Free Survival
Oocytes
Blood Proteins
Membrane Proteins
Epithelial Cells
Cell Membrane
Kidney

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Na+/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer : Molecular characterization of SMCT. / Paroder, Viktoriya; Spencer, Shelly R.; Paroder, Monika; Arango, Diego; Schwartz, Simo; Mariadason, John M.; Augenlicht, Leonard H.; Eskandari, Sepehr; Carrasco, Nancy.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 19, 09.05.2006, p. 7270-7275.

Research output: Contribution to journalArticle

Paroder, Viktoriya ; Spencer, Shelly R. ; Paroder, Monika ; Arango, Diego ; Schwartz, Simo ; Mariadason, John M. ; Augenlicht, Leonard H. ; Eskandari, Sepehr ; Carrasco, Nancy. / Na+/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer : Molecular characterization of SMCT. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 19. pp. 7270-7275.
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