PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure
Though homotypic cell-in-cell (hoCIC) structures are implicated in the development and progression of multiple human tumors, the molecular mechanisms underlying their formation remain poorly understood. We found that the expression of Protocadherin-7 (PCDH7), an integral membrane protein, was negati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00329/full |
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| author | Chenxi Wang Chenxi Wang Ang Chen Banzhan Ruan Banzhan Ruan Zubiao Niu Yan Su Hongquan Qin You Zheng Bo Zhang Lihua Gao Zhaolie Chen Hongyan Huang Xiaoning Wang Xiaoning Wang Qiang Sun |
| author_facet | Chenxi Wang Chenxi Wang Ang Chen Banzhan Ruan Banzhan Ruan Zubiao Niu Yan Su Hongquan Qin You Zheng Bo Zhang Lihua Gao Zhaolie Chen Hongyan Huang Xiaoning Wang Xiaoning Wang Qiang Sun |
| author_sort | Chenxi Wang |
| collection | DOAJ |
| description | Though homotypic cell-in-cell (hoCIC) structures are implicated in the development and progression of multiple human tumors, the molecular mechanisms underlying their formation remain poorly understood. We found that the expression of Protocadherin-7 (PCDH7), an integral membrane protein, was negatively associated with the formation of hoCIC structures. Overexpression of PCDH7 efficiently inhibits, while its depletion significantly enhances, hoCIC formation, which was attributed to its regulation on intercellular adhesion and contractile actomyosin as well. Via directly interacting with and inactivating PP1α, a protein phosphatase that dephosphorylates pMLC2, PCDH7 increases the level of pMLC2 leading to enhanced actomyosin at the intercellular region and compromised hoCIC formation. Remarkably, PCDH7 enhanced anchorage-independent cell growth in a hoCIC-dependent manner. Together, we identified PCDH7 as the first trans-membrane protein that inhibits hoCIC formation to promote tumor growth. |
| first_indexed | 2024-12-12T21:32:01Z |
| format | Article |
| id | doaj.art-0e3ad9d64c88461cb8c0611d96a253c4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T21:32:01Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0e3ad9d64c88461cb8c0611d96a253c42022-12-22T00:11:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-05-01810.3389/fcell.2020.00329531878PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell StructureChenxi Wang0Chenxi Wang1Ang Chen2Banzhan Ruan3Banzhan Ruan4Zubiao Niu5Yan Su6Hongquan Qin7You Zheng8Bo Zhang9Lihua Gao10Zhaolie Chen11Hongyan Huang12Xiaoning Wang13Xiaoning Wang14Qiang Sun15School of Biology and Biological Engineering, South China University of Technology, Guangzhou, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaDepartment of Biology, Hainan Medical University, Haikou, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaDepartment of Oncology, Capital Medical University, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaDepartment of Oncology, Capital Medical University, Beijing, ChinaSchool of Biology and Biological Engineering, South China University of Technology, Guangzhou, ChinaBeijing Key Laboratory of Aging and Geriatrics, Chinese PLA General Hospital, Beijing, ChinaLaboratory of Cell Engineering, Institute of Biotechnology, Beijing, ChinaThough homotypic cell-in-cell (hoCIC) structures are implicated in the development and progression of multiple human tumors, the molecular mechanisms underlying their formation remain poorly understood. We found that the expression of Protocadherin-7 (PCDH7), an integral membrane protein, was negatively associated with the formation of hoCIC structures. Overexpression of PCDH7 efficiently inhibits, while its depletion significantly enhances, hoCIC formation, which was attributed to its regulation on intercellular adhesion and contractile actomyosin as well. Via directly interacting with and inactivating PP1α, a protein phosphatase that dephosphorylates pMLC2, PCDH7 increases the level of pMLC2 leading to enhanced actomyosin at the intercellular region and compromised hoCIC formation. Remarkably, PCDH7 enhanced anchorage-independent cell growth in a hoCIC-dependent manner. Together, we identified PCDH7 as the first trans-membrane protein that inhibits hoCIC formation to promote tumor growth.https://www.frontiersin.org/article/10.3389/fcell.2020.00329/fullPCDH7cell-in-cell structureadherens junctionsactomyosinpMLC2 |
| spellingShingle | Chenxi Wang Chenxi Wang Ang Chen Banzhan Ruan Banzhan Ruan Zubiao Niu Yan Su Hongquan Qin You Zheng Bo Zhang Lihua Gao Zhaolie Chen Hongyan Huang Xiaoning Wang Xiaoning Wang Qiang Sun PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure Frontiers in Cell and Developmental Biology PCDH7 cell-in-cell structure adherens junctions actomyosin pMLC2 |
| title | PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure |
| title_full | PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure |
| title_fullStr | PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure |
| title_full_unstemmed | PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure |
| title_short | PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure |
| title_sort | pcdh7 inhibits the formation of homotypic cell in cell structure |
| topic | PCDH7 cell-in-cell structure adherens junctions actomyosin pMLC2 |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00329/full |
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