Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells

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This article evaluates the effects of enforced overexpression of two known G protein-coupled receptors in two phenotypically distinct breast cancer cell lines.

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16 p.

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Thirunavukkarasan, Madhumathi; Wang, Chao; Rao, Angad; Hind, Tatsuma; Teo, Yuan Ru; Siddiquee, Abrar Al-Mahmood et al. October 19, 2017.

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This article evaluates the effects of enforced overexpression of two known G protein-coupled receptors in two phenotypically distinct breast cancer cell lines.

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16 p.

Notes

Abstract: Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are present in
human plasma at micromolar concentrations. In addition to serving as metabolic precursors
for lipid and carbohydrate synthesis, they also act as cognate ligands for two known G protein-
coupled receptors (GPCRs), FFAR2 and FFAR3. While there is evidence that these
receptors may inhibit the progression of colorectal cancer, their roles in breast cancer cells
are largely unknown. We evaluated the effects of enforced overexpression of these receptors
in two phenotypically distinct breast cancer cell lines: MCF7 and MDA-MD-231. Our
results demonstrate that both receptors inhibit cell invasiveness, but through different signaling
processes. In invasive, mesenchymal-like MDA-MB-231 cells, FFAR2 inhibits the
Hippo-Yap pathway and increases expression of adhesion protein E-cadherin, while FFAR3
inhibits MAPK signaling. Both receptors have the net effect of reducing actin polymerization
and invasion of cells through a Matrigel matrix. These effects were absent in the less invasive,
epithelial-like MCF7 cells. Correspondingly, there is reduced expression of both receptors
in invasive breast carcinoma and in aggressive triple-negative breast tumors, relative to
normal breast tissue. Cumulatively, our data suggest that the activation of cognate receptors
by short chain fatty acids drives breast cancer cells toward a non-invasive phenotype and
therefore may inhibit metastasis.

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  • PLOS ONE, 2017. San Francisco, CA: Public Library of Science

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  • Publication Title: PLOS ONE
  • Volume: 12
  • Issue: 10
  • Pages: 1-16
  • Peer Reviewed: Yes

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UNT Scholarly Works

Materials from the UNT community's research, creative, and scholarly activities and UNT's Open Access Repository. Access to some items in this collection may be restricted.

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  • June 1, 2017

Accepted Date

  • October 1, 2017

Creation Date

  • October 19, 2017

Added to The UNT Digital Library

  • Nov. 15, 2017, 11:13 a.m.

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Thirunavukkarasan, Madhumathi; Wang, Chao; Rao, Angad; Hind, Tatsuma; Teo, Yuan Ru; Siddiquee, Abrar Al-Mahmood et al. Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells, article, October 19, 2017; San Francisco, California. (digital.library.unt.edu/ark:/67531/metadc1040544/: accessed December 13, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.