GIT1 protects against breast cancer growth through negative regulation of Notch

doi:10.1038/s41467-022-28631-y

KMS > 免疫化学研究所 > PI研究组 > Katsuhiko Mikoshiba组

	GIT1 protects against breast cancer growth through negative regulation of Notch
	Zhang, Songbai 1; Miyakawa, Ayako 1,2; Wickström, Malin 3; Dyberg, Cecilia 3; Louhivuori, Lauri 1; Varas-Godoy, Manuel 1,4; Kemppainen, Kati 5,6; Kanatani, Shigeaki 1; Kaczynska, Dagmara 1; Ellström, Ivar Dehnisch 1; Elfman, Lotta 3; Kronqvist, Pauliina 7; Repo, Heli 7; Mikoshiba, Katsuhiko8,9,10 ; Sahlgren, Cecilia 5,6,11; Johnsen, John Inge 3; Uhlén, Per 1
	2022-12-01
发表期刊	NATURE COMMUNICATIONS
EISSN	2041-1723
卷号	13 期号:1
发表状态	已发表
DOI	10.1038/s41467-022-28631-y
摘要	Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch. GIT1 knockdown in ER(-) breast tumour cells increased signalling downstream of Notch and activity of aldehyde dehydrogenase, a predictor of poor clinical outcome. GIT1 interacts with the Notch intracellular domain (ICD) and influences signalling by inhibiting the cytoplasm-to-nucleus transport of the Notch ICD. In xenograft experiments, overexpression of GIT1 in ER(-) cells prevented or reduced Notch-driven tumour formation. These results identify GIT1 as a modulator of Notch signalling and a guardian against breast cancer growth.
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收录类别	SCIE
语种	英语
Scopus 记录号	2-s2.0-85126804773
来源库	Scopus
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/169256
专题	免疫化学研究所_PI研究组_Katsuhiko Mikoshiba组
作者单位	1.Department of Medical Biochemistry and Biophysics,Karolinska Institutet,Stockholm,Sweden 2.Department of Molecular Medicine and Surgery,Karolinska University Hospital,Stockholm,Sweden 3.Department of Women’s and Children’s Health,Karolinska Institutet,Stockholm,Sweden 4.Centro de Biología Celular y Biomedicina (CEBICEM),Facultad de Medicina y Ciencia,Universidad San Sebastián,Santiago,Chile 5.Turku Bioscience,Åbo Akademi University and University of Turku,Turku,Finland 6.Faculty of Science and Engineering,Åbo Akademi University,Turku,Finland 7.Department of Pathology,University of Turku,Turku,Finland 8.Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai,China 9.RIKEN Center for Life Science Technologies (CLST),Chuo-ku,Kobe,Japan 10.Department of Biomolecular Science,Faculty of Science,Toho University,Chiba,Japan 11.Institute for Complex Molecular Systems,Eindhoven University of Technology,Eindhoven,Netherlands
推荐引用方式 GB/T 7714	Zhang, Songbai,Miyakawa, Ayako,Wickström, Malin,et al. GIT1 protects against breast cancer growth through negative regulation of Notch[J]. NATURE COMMUNICATIONS,2022,13(1).
APA	Zhang, Songbai.,Miyakawa, Ayako.,Wickström, Malin.,Dyberg, Cecilia.,Louhivuori, Lauri.,...&Uhlén, Per.(2022).GIT1 protects against breast cancer growth through negative regulation of Notch.NATURE COMMUNICATIONS,13(1).
MLA	Zhang, Songbai,et al."GIT1 protects against breast cancer growth through negative regulation of Notch".NATURE COMMUNICATIONS 13.1(2022).