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The interactions of...
The interactions of Bcl9/Bcl9L with beta-catenin and Pygopus promote breast cancer growth, invasion, and metastasis
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- Vafaizadeh, Vida (författare)
- Univ Basel, Switzerland
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- Buechel, David (författare)
- Univ Basel, Switzerland
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- Rubinstein, Natalia (författare)
- Univ Buenos Aires, Argentina
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- Kalathur, Ravi K. R. (författare)
- Univ Basel, Switzerland; Royal Childrens Hosp, Australia
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- Bazzani, Lorenzo (författare)
- Univ Basel, Switzerland; Univ Siena, Italy
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- Saxena, Meera (författare)
- Univ Basel, Switzerland
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- Valenta, Tomas (författare)
- Univ Zurich, Switzerland
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- Hausmann, George (författare)
- Univ Zurich, Switzerland
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- Cantù, Claudio, 1981- (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Wallenberg Ctr Mol Med
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- Basler, Konrad (författare)
- Univ Zurich, Switzerland
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- Christofori, Gerhard (författare)
- Univ Basel, Switzerland
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(creator_code:org_t)
- 2021-09-20
- 2021
- Engelska.
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Ingår i: Oncogene. - : Springer Nature. - 0950-9232 .- 1476-5594. ; 40:43, s. 6195-6209
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Canonical Wnt/beta-catenin signaling is an established regulator of cellular state and its critical contributions to tumor initiation, malignant tumor progression and metastasis formation have been demonstrated in various cancer types. Here, we investigated how the binding of beta-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) and Bcl9-Like (Bcl9L) affected mammary gland carcinogenesis in the MMTV-PyMT transgenic mouse model of metastatic breast cancer. Conditional knockout of both Bcl9 and Bcl9L resulted into tumor cell death. In contrast, disrupting the interaction of Bcl9/Bcl9L with beta-catenin, either by deletion of their HD2 domains or by a point mutation in the N-terminal domain of beta-catenin (D164A), diminished primary tumor growth and tumor cell proliferation and reduced tumor cell invasion and lung metastasis. In comparison, the disruption of HD1 domain-mediated binding of Bcl9/Bcl9L to Pygopus had only moderate effects. Interestingly, interfering with the beta-catenin-Bcl9/Bcl9L-Pygo chain of adapters only partially impaired the transcriptional response of mammary tumor cells to Wnt3a and TGF beta treatments. Together, the results indicate that Bcl9/Bcl9L modulate but are not critically required for canonical Wnt signaling in its contribution to breast cancer growth and malignant progression, a notion consistent with the "just-right" hypothesis of Wnt-driven tumor progression.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (ämneskategori)
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Oncogene
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Vafaizadeh, Vida
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Buechel, David
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Rubinstein, Nata ...
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Kalathur, Ravi K ...
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Bazzani, Lorenzo
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Saxena, Meera
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Valenta, Tomas
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Hausmann, George
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Cantù, Claudio, ...
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Basler, Konrad
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Christofori, Ger ...
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Oncogene
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