Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis

Abstract Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore...

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Main Authors: Yu Ri Seo, Junghyeon Lee, Han Suk Ryu, EunHee G. Kim, So Hyun Kim, Jieun Jeong, Hyeryeon Jung, YeoJin Jung, Han Byeol Kim, Yeon Hui Jo, Yeong Dong Kim, Min-Sun Jin, Yong Yook Lee, Kristine M. Kim, Eugene C. Yi
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-41416-7
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author Yu Ri Seo
Junghyeon Lee
Han Suk Ryu
EunHee G. Kim
So Hyun Kim
Jieun Jeong
Hyeryeon Jung
YeoJin Jung
Han Byeol Kim
Yeon Hui Jo
Yeong Dong Kim
Min-Sun Jin
Yong Yook Lee
Kristine M. Kim
Eugene C. Yi
author_facet Yu Ri Seo
Junghyeon Lee
Han Suk Ryu
EunHee G. Kim
So Hyun Kim
Jieun Jeong
Hyeryeon Jung
YeoJin Jung
Han Byeol Kim
Yeon Hui Jo
Yeong Dong Kim
Min-Sun Jin
Yong Yook Lee
Kristine M. Kim
Eugene C. Yi
author_sort Yu Ri Seo
collection DOAJ
description Abstract Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.
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spelling doaj.art-57b613c0a0214fe69b00b7717f0c27952023-11-19T12:57:18ZengNature PortfolioScientific Reports2045-23222023-08-0113111410.1038/s41598-023-41416-7Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysisYu Ri Seo0Junghyeon Lee1Han Suk Ryu2EunHee G. Kim3So Hyun Kim4Jieun Jeong5Hyeryeon Jung6YeoJin Jung7Han Byeol Kim8Yeon Hui Jo9Yeong Dong Kim10Min-Sun Jin11Yong Yook Lee12Kristine M. Kim13Eugene C. Yi14Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Bio-Health Convergence, Kangwon National UniversityDepartment of Pathology, Seoul National University Hospital, College of Medicine, Seoul National UniversityDepartment of Systems Immunology, Division of Biomedical Convergence, College of Biomedical Science, Kangwon National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Systems Immunology, Division of Biomedical Convergence, College of Biomedical Science, Kangwon National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Systems Immunology, Division of Biomedical Convergence, College of Biomedical Science, Kangwon National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Bio-Health Convergence, Kangwon National UniversityDepartment of Bio-Health Convergence, Kangwon National UniversityDepartment of Pathology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Bio-Health Convergence, Kangwon National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityAbstract Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.https://doi.org/10.1038/s41598-023-41416-7
spellingShingle Yu Ri Seo
Junghyeon Lee
Han Suk Ryu
EunHee G. Kim
So Hyun Kim
Jieun Jeong
Hyeryeon Jung
YeoJin Jung
Han Byeol Kim
Yeon Hui Jo
Yeong Dong Kim
Min-Sun Jin
Yong Yook Lee
Kristine M. Kim
Eugene C. Yi
Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
Scientific Reports
title Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
title_full Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
title_fullStr Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
title_full_unstemmed Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
title_short Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis
title_sort lateral interactions between cd276 and cd147 are essential for stemness in breast cancer a novel insight from proximal proteome analysis
url https://doi.org/10.1038/s41598-023-41416-7
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