GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer
Breast cancer is one of the most common types of malignancy worldwide; however, its underlying mechanisms remain unclear. In the present study, we investigated the roles of G-protein-coupled receptor family C, member 5, group A (GPRC5A) in cell apoptosis in triple-negative breast cancer (TNBC). The...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.624493/full |
| _version_ | 1818662455421698048 |
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| author | Lu Yang Lu Yang Lu Yang Lu Yang Shaorong Zhao Shaorong Zhao Shaorong Zhao Shaorong Zhao Tong Zhu Tong Zhu Tong Zhu Tong Zhu Jin Zhang Jin Zhang Jin Zhang Jin Zhang |
| author_facet | Lu Yang Lu Yang Lu Yang Lu Yang Shaorong Zhao Shaorong Zhao Shaorong Zhao Shaorong Zhao Tong Zhu Tong Zhu Tong Zhu Tong Zhu Jin Zhang Jin Zhang Jin Zhang Jin Zhang |
| author_sort | Lu Yang |
| collection | DOAJ |
| description | Breast cancer is one of the most common types of malignancy worldwide; however, its underlying mechanisms remain unclear. In the present study, we investigated the roles of G-protein-coupled receptor family C, member 5, group A (GPRC5A) in cell apoptosis in triple-negative breast cancer (TNBC). The expression of GPRC5A in breast cancer cell lines was detected by real time PCR and western blot. And the results suggested that GPRC5A was downregulated in breast cancer cell lines compared to normal breast epithelial cell lines. Additionally, the expression of GPRC5A in TCGA database was analyzed in silico. GPRC5A exhibited the lowest expression levels in TNBC compared to ER+ and HER2+ breast cancer. Overexpression of GPRC5A in MDA-MB-231 and MDA-MB-468 cells promoted apoptosis, whereas depletion of GPRC5A in T47D and MCF7 cells inhibited cell apoptosis via the intrinsic apoptotic pathway. We performed RNA-sequencing in GPRC5A overexpressed MDA-MB-231 and the control cells. The results facilitated the identification of a number of signaling pathways involved in this process, and the PI3K/Akt signaling pathway was found to be one the most important. A specific activator of the PI3K/Akt signaling pathway inhibited apoptosis of breast cancer cells, whereas cotreatment of this activator with a GPRC5A-expressing plasmid reduced this effect. Similarly, a specific inhibitor of the PI3K/Akt signaling pathway increased cell apoptosis by activating caspase-3 and caspase-9, whereas co-incubation of the inhibitor with a short hairpin RNA targeting GPRC5A significantly reduced the cell apoptotic rate. Additionally, the overexpression of GPRC5A suppressed tumor growth by inducing cell apoptosis in vivo. Taken together, the present study identified GPRC5A as a protective factor against the progression of human triple-negative breast cancer by increasing cell apoptosis via the regulation of the PI3K/Akt signaling pathway. |
| first_indexed | 2024-12-17T05:01:13Z |
| format | Article |
| id | doaj.art-a70c3e284cbd408b950dc4fc61183f3f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T05:01:13Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a70c3e284cbd408b950dc4fc61183f3f2022-12-21T22:02:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.624493624493GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast CancerLu Yang0Lu Yang1Lu Yang2Lu Yang3Shaorong Zhao4Shaorong Zhao5Shaorong Zhao6Shaorong Zhao7Tong Zhu8Tong Zhu9Tong Zhu10Tong Zhu11Jin Zhang12Jin Zhang13Jin Zhang14Jin Zhang15The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaKey Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaTianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaKey Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, ChinaThe Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaKey Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaTianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaKey Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, ChinaThe Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaKey Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaTianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaKey Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, ChinaThe Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaKey Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaTianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaKey Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, ChinaBreast cancer is one of the most common types of malignancy worldwide; however, its underlying mechanisms remain unclear. In the present study, we investigated the roles of G-protein-coupled receptor family C, member 5, group A (GPRC5A) in cell apoptosis in triple-negative breast cancer (TNBC). The expression of GPRC5A in breast cancer cell lines was detected by real time PCR and western blot. And the results suggested that GPRC5A was downregulated in breast cancer cell lines compared to normal breast epithelial cell lines. Additionally, the expression of GPRC5A in TCGA database was analyzed in silico. GPRC5A exhibited the lowest expression levels in TNBC compared to ER+ and HER2+ breast cancer. Overexpression of GPRC5A in MDA-MB-231 and MDA-MB-468 cells promoted apoptosis, whereas depletion of GPRC5A in T47D and MCF7 cells inhibited cell apoptosis via the intrinsic apoptotic pathway. We performed RNA-sequencing in GPRC5A overexpressed MDA-MB-231 and the control cells. The results facilitated the identification of a number of signaling pathways involved in this process, and the PI3K/Akt signaling pathway was found to be one the most important. A specific activator of the PI3K/Akt signaling pathway inhibited apoptosis of breast cancer cells, whereas cotreatment of this activator with a GPRC5A-expressing plasmid reduced this effect. Similarly, a specific inhibitor of the PI3K/Akt signaling pathway increased cell apoptosis by activating caspase-3 and caspase-9, whereas co-incubation of the inhibitor with a short hairpin RNA targeting GPRC5A significantly reduced the cell apoptotic rate. Additionally, the overexpression of GPRC5A suppressed tumor growth by inducing cell apoptosis in vivo. Taken together, the present study identified GPRC5A as a protective factor against the progression of human triple-negative breast cancer by increasing cell apoptosis via the regulation of the PI3K/Akt signaling pathway.https://www.frontiersin.org/articles/10.3389/fonc.2020.624493/fullG-protein-coupled receptor family Cmember 5group A (Gprc5a)cell apoptosisPI3K/Aktbreast cancer |
| spellingShingle | Lu Yang Lu Yang Lu Yang Lu Yang Shaorong Zhao Shaorong Zhao Shaorong Zhao Shaorong Zhao Tong Zhu Tong Zhu Tong Zhu Tong Zhu Jin Zhang Jin Zhang Jin Zhang Jin Zhang GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer Frontiers in Oncology G-protein-coupled receptor family C member 5 group A (Gprc5a) cell apoptosis PI3K/Akt breast cancer |
| title | GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer |
| title_full | GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer |
| title_fullStr | GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer |
| title_full_unstemmed | GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer |
| title_short | GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer |
| title_sort | gprc5a is a negative regulator of the pro survival pi3k akt signaling pathway in triple negative breast cancer |
| topic | G-protein-coupled receptor family C member 5 group A (Gprc5a) cell apoptosis PI3K/Akt breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.624493/full |
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