气候变化领域集成服务门户(CCPortal): Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression

CCPortal

DOI	10.1073/pnas.2020227118
	Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression
	Buechel D.; Sugiyama N.; Rubinstein N.; Saxena M.; Kalathur R.K.R.; Lüönd F.; Vafaizadeh V.; Valenta T.; Hausmann G.; Cantù C.; Basler K.; Christofori G.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:34
英文摘要	During malignant progression, epithelial cancer cells dissolve their cell–cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell–cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of β-catenin’s transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)–PyMT mouse model of metastatic breast cancer, we compared the complete elimination of β-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of β-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of β-catenin’s transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial–mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by β-catenin’s transcriptional activities upon stimulation with Wnt3a or during TGF-β–induced EMT. Our results uncouple the signaling from the adhesion function of β-catenin and underline the importance of Wnt/β-catenin–dependent transcription in malignant tumor progression of breast cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Breast cancer; Cell adhesion; Metastasis; Wnt signaling; β-catenin
语种	英语
scopus关键词	beta catenin; transcriptome; transforming growth factor beta; Wnt3a protein; Wnt3a protein, mouse; animal; apoptosis; cell adhesion; cell cycle; cell motion; drug effect; epithelial mesenchymal transition; experimental mammary neoplasm; female; gene expression regulation; genetics; metabolism; metastasis; mouse; physiology; signal transduction; transgenic mouse; tumor invasion; Animals; Apoptosis; beta Catenin; Cell Adhesion; Cell Cycle; Cell Movement; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Mammary Neoplasms, Animal; Mice; Mice, Transgenic; Neoplasm Invasiveness; Neoplasm Metastasis; Signal Transduction; Transcriptome; Transforming Growth Factor beta; Wnt3A Protein
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251045
作者单位	Department of Biomedicine, University of Basel, Basel, 4031, Switzerland; Instituto de Biociencias, Biotecnología y Biología Traslacional, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, 2160, Argentina; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Molecular Life Sciences, University of Zürich, Zürich, 8057, Switzerland; Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, 581 83, Sweden; Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Faculty of Medicine and Health Sciences, Linköping University, Linköping, 581 83, Sweden
推荐引用方式 GB/T 7714	Buechel D.,Sugiyama N.,Rubinstein N.,等. Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression[J],2021,118(34).
APA	Buechel D..,Sugiyama N..,Rubinstein N..,Saxena M..,Kalathur R.K.R..,...&Christofori G..(2021).Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression.Proceedings of the National Academy of Sciences of the United States of America,118(34).
MLA	Buechel D.,et al."Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression".Proceedings of the National Academy of Sciences of the United States of America 118.34(2021).