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Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system
Li, Koukou1; Wu, Renfei1; Zhou, Muya1; Tong, Haibo1; Luo, Kathy Qian1,2
2021-10-01
Source PublicationScience Advances
ISSN2375-2548
Volume7Issue:40Pages:eabg7265
Abstract

To study how cancer cells can withstand fluid shear stress (SS), we isolated SS-resistant breast and lung cancer cells using a microfluidic circulatory system. These SS-resistant cells showed higher abilities to form clusters, survive in circulation, and metastasize in mice. These SS-resistant cells expressed 4.2- to 5.3-fold more desmocollin-2 (DSC2) and plakophilin-1 (PKP1) proteins. The high expression of DSC2 and PKP1 facilitated cancer cells to form clusters in circulation, and also activated PI3K/AKT/Bcl-2-mediated pathway to increase cell survival. The high levels of DSC2 and PKP1 are also important for maintaining high expression of vimentin, which stimulates fibronectin/ integrin β1/FAK/Src/MEK/ERK/ZEB1-mediated metastasis. Moreover, higher levels of DSC2 and PKP1 were detected in tumor samples from patients with breast and lung cancer, and their high expression was correlated with lower overall survival and worse disease progression. DSC2 and PKP1 may serve as new biomarkers for detecting and targeting metastatic circulating tumor cells.

DOI10.1126/sciadv.abg7265
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000703091100007
Scopus ID2-s2.0-85116370057
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLuo, Kathy Qian
Affiliation1.Faculty of Health Sciences, University of Macau, Taipa, Macao
2.Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences;  University of Macau
Recommended Citation
GB/T 7714
Li, Koukou,Wu, Renfei,Zhou, Muya,et al. Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system[J]. Science Advances,2021,7(40):eabg7265.
APA Li, Koukou,Wu, Renfei,Zhou, Muya,Tong, Haibo,&Luo, Kathy Qian.(2021).Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system.Science Advances,7(40),eabg7265.
MLA Li, Koukou,et al."Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system".Science Advances 7.40(2021):eabg7265.
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