Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion
Integrin α3β1, a cell adhesion receptor for certain laminins, is known to promote breast tumor growth and invasion. Our previous gene microarray study showed that the RELN gene, which encodes the extracellular glycoprotein Reelin, was upregulated in α3β1-deficient (i.e., α3 knockdown) MDA-MB-231 cel...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/2/344 |
| _version_ | 1797409974533488640 |
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| author | Abibatou Ndoye Rakshitha Pandulal Miskin C. Michael DiPersio |
| author_facet | Abibatou Ndoye Rakshitha Pandulal Miskin C. Michael DiPersio |
| author_sort | Abibatou Ndoye |
| collection | DOAJ |
| description | Integrin α3β1, a cell adhesion receptor for certain laminins, is known to promote breast tumor growth and invasion. Our previous gene microarray study showed that the RELN gene, which encodes the extracellular glycoprotein Reelin, was upregulated in α3β1-deficient (i.e., α3 knockdown) MDA-MB-231 cells. In breast cancer, reduced RELN expression is associated with increased invasion and poor prognosis. In this study we demonstrate that α3β1 represses RELN expression to enhance breast cancer cell invasion. RELN mRNA was significantly increased upon RNAi-mediated α3 knockdown in two triple-negative breast cancer cell lines, MDA-MB-231 and SUM159. Modulation of baseline Reelin levels altered invasive potential, where enhanced Reelin expression in MDA-MB-231 cells reduced invasion, while RNAi-mediated suppression of Reelin in SUM159 cells increased invasion. Moreover, treatment of α3β1-expressing MDA-MB-231 cells with culture medium that was conditioned by α3 knockdown MDA-MB-231 cells led to decreased invasion. RNAi-mediated suppression of Reelin in α3 knockdown MDA-MB-231 cells mitigated this effect of conditioned-medium, identifying secreted Reelin as an inhibitor of cell invasion. These results demonstrate a novel role for α3β1 in repressing Reelin in breast cancer cells to promote invasion, supporting this integrin as a potential therapeutic target. |
| first_indexed | 2024-03-09T04:23:11Z |
| format | Article |
| id | doaj.art-b117fa6fa177478ea203eba2ec187395 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:23:11Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b117fa6fa177478ea203eba2ec1873952023-12-03T13:44:46ZengMDPI AGCancers2072-66942021-01-0113234410.3390/cancers13020344Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote InvasionAbibatou Ndoye0Rakshitha Pandulal Miskin1C. Michael DiPersio2Department of Surgery, Albany Medical College, Albany, 12208 NY, USADepartment of Regenerative and Cancer Cell Biology, Albany Medical College, Albany 12208, NY, USADepartment of Surgery, Albany Medical College, Albany, 12208 NY, USAIntegrin α3β1, a cell adhesion receptor for certain laminins, is known to promote breast tumor growth and invasion. Our previous gene microarray study showed that the RELN gene, which encodes the extracellular glycoprotein Reelin, was upregulated in α3β1-deficient (i.e., α3 knockdown) MDA-MB-231 cells. In breast cancer, reduced RELN expression is associated with increased invasion and poor prognosis. In this study we demonstrate that α3β1 represses RELN expression to enhance breast cancer cell invasion. RELN mRNA was significantly increased upon RNAi-mediated α3 knockdown in two triple-negative breast cancer cell lines, MDA-MB-231 and SUM159. Modulation of baseline Reelin levels altered invasive potential, where enhanced Reelin expression in MDA-MB-231 cells reduced invasion, while RNAi-mediated suppression of Reelin in SUM159 cells increased invasion. Moreover, treatment of α3β1-expressing MDA-MB-231 cells with culture medium that was conditioned by α3 knockdown MDA-MB-231 cells led to decreased invasion. RNAi-mediated suppression of Reelin in α3 knockdown MDA-MB-231 cells mitigated this effect of conditioned-medium, identifying secreted Reelin as an inhibitor of cell invasion. These results demonstrate a novel role for α3β1 in repressing Reelin in breast cancer cells to promote invasion, supporting this integrin as a potential therapeutic target.https://www.mdpi.com/2072-6694/13/2/344integrin α3β1ReelinRELNtumor microenvironmentcancer cell secretomeinvasion |
| spellingShingle | Abibatou Ndoye Rakshitha Pandulal Miskin C. Michael DiPersio Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion Cancers integrin α3β1 Reelin RELN tumor microenvironment cancer cell secretome invasion |
| title | Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion |
| title_full | Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion |
| title_fullStr | Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion |
| title_full_unstemmed | Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion |
| title_short | Integrin α3β1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion |
| title_sort | integrin α3β1 represses reelin expression in breast cancer cells to promote invasion |
| topic | integrin α3β1 Reelin RELN tumor microenvironment cancer cell secretome invasion |
| url | https://www.mdpi.com/2072-6694/13/2/344 |
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