Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells
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 (GPC...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Public Library of Science
2017
|
| Online Access: | http://hdl.handle.net/20.500.11937/58006 |
| _version_ | 1848760153472499712 |
|---|---|
| author | Thirunavukkarasan, M. Wang, C. Rao, A. Hind, T. Teo, Y. Siddiquee, A. Goghari, M. Kumar, Alan Prem Herr, D. |
| author_facet | Thirunavukkarasan, M. Wang, C. Rao, A. Hind, T. Teo, Y. Siddiquee, A. Goghari, M. Kumar, Alan Prem Herr, D. |
| author_sort | Thirunavukkarasan, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. © 2017 Thirunavukkarasan et al. |
| first_indexed | 2025-11-14T10:11:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-58006 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:11:15Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-580062018-01-12T03:55:09Z Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells Thirunavukkarasan, M. Wang, C. Rao, A. Hind, T. Teo, Y. Siddiquee, A. Goghari, M. Kumar, Alan Prem Herr, D. 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. © 2017 Thirunavukkarasan et al. 2017 Journal Article http://hdl.handle.net/20.500.11937/58006 10.1371/journal.pone.0186334 http://creativecommons.org/licenses/by/4.0/ Public Library of Science fulltext |
| spellingShingle | Thirunavukkarasan, M. Wang, C. Rao, A. Hind, T. Teo, Y. Siddiquee, A. Goghari, M. Kumar, Alan Prem Herr, D. Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title | Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title_full | Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title_fullStr | Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title_full_unstemmed | Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title_short | Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| title_sort | short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells |
| url | http://hdl.handle.net/20.500.11937/58006 |