CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate
Ovarian cancer is a leading cause of death from gynecologic malignancies worldwide. Although CD83 is widely described as a solid marker for mature dendritic cells, emerging pieces of evidence indicate the expression of membrane protein CD83 by various tumor cells, including ovarian cancer cells. How...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2269 |
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| author | Aalia Batool Hao Liu Yi-Xun Liu Su-Ren Chen |
| author_facet | Aalia Batool Hao Liu Yi-Xun Liu Su-Ren Chen |
| author_sort | Aalia Batool |
| collection | DOAJ |
| description | Ovarian cancer is a leading cause of death from gynecologic malignancies worldwide. Although CD83 is widely described as a solid marker for mature dendritic cells, emerging pieces of evidence indicate the expression of membrane protein CD83 by various tumor cells, including ovarian cancer cells. However, the potential role of CD83 in ovarian cancer cell properties and development remains absolutely unknown. By using human CD83 stable overexpression and knockdown sublines of several ovarian cancer cells, we observed that CD83 advanced the growth proliferation, colony formation ability, spheroid formation, and in vivo tumorigenicity of ovarian cancer cells; surprisingly, CD83 limited their migration and invasion potentials. Positive regulation of proliferation/stemness factors (e.g., cyclin-CDKs and KIT/CD44) but negative regulation of matrix metallopeptidases (e.g., MMP1 and 7) by CD83 were revealed by the integrated analysis of transcriptome and proteome. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) first identified the association of CD83 with MAP3K7 (also known as TAK1) and MAP3K7-binding protein TAB1 on the cell membrane. Moreover, CD83 functions through the activation of MAP3K7-MEK1/2-ERK1/2 cascades to further regulate downstream FOXO1/p21/CDK2/CCNB1 and STAT3/DKK1 signaling pathways, thus activating proliferation and spheroid formation of ovarian cancer cells, respectively. Collectively, our findings define a CD83-MAPK pathway in the regulation of proliferation and stemness in ovarian cancer cells, with potential therapeutic applications in blocking their progression. |
| first_indexed | 2024-03-10T17:30:33Z |
| format | Article |
| id | doaj.art-4ae4aaf5c1994f68a4a120dcc0ff2722 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T17:30:33Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4ae4aaf5c1994f68a4a120dcc0ff27222023-11-20T10:01:16ZengMDPI AGCancers2072-66942020-08-01128226910.3390/cancers12082269CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell FateAalia Batool0Hao Liu1Yi-Xun Liu2Su-Ren Chen3Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, ChinaLaboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinaLaboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, ChinaOvarian cancer is a leading cause of death from gynecologic malignancies worldwide. Although CD83 is widely described as a solid marker for mature dendritic cells, emerging pieces of evidence indicate the expression of membrane protein CD83 by various tumor cells, including ovarian cancer cells. However, the potential role of CD83 in ovarian cancer cell properties and development remains absolutely unknown. By using human CD83 stable overexpression and knockdown sublines of several ovarian cancer cells, we observed that CD83 advanced the growth proliferation, colony formation ability, spheroid formation, and in vivo tumorigenicity of ovarian cancer cells; surprisingly, CD83 limited their migration and invasion potentials. Positive regulation of proliferation/stemness factors (e.g., cyclin-CDKs and KIT/CD44) but negative regulation of matrix metallopeptidases (e.g., MMP1 and 7) by CD83 were revealed by the integrated analysis of transcriptome and proteome. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) first identified the association of CD83 with MAP3K7 (also known as TAK1) and MAP3K7-binding protein TAB1 on the cell membrane. Moreover, CD83 functions through the activation of MAP3K7-MEK1/2-ERK1/2 cascades to further regulate downstream FOXO1/p21/CDK2/CCNB1 and STAT3/DKK1 signaling pathways, thus activating proliferation and spheroid formation of ovarian cancer cells, respectively. Collectively, our findings define a CD83-MAPK pathway in the regulation of proliferation and stemness in ovarian cancer cells, with potential therapeutic applications in blocking their progression.https://www.mdpi.com/2072-6694/12/8/2269ovarian cancerproliferationstemnessCD83MAPK signaling pathwayMAP3K7 |
| spellingShingle | Aalia Batool Hao Liu Yi-Xun Liu Su-Ren Chen CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate Cancers ovarian cancer proliferation stemness CD83 MAPK signaling pathway MAP3K7 |
| title | CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate |
| title_full | CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate |
| title_fullStr | CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate |
| title_full_unstemmed | CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate |
| title_short | CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate |
| title_sort | cd83 a novel mapk signaling pathway interactor determines ovarian cancer cell fate |
| topic | ovarian cancer proliferation stemness CD83 MAPK signaling pathway MAP3K7 |
| url | https://www.mdpi.com/2072-6694/12/8/2269 |
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