Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis
Open accessAbstract
Metastatic disease is the primary cause of death in breast cancer, the most common malignancy in Western women. Loss of E-cadherin is associated with tumor metastasis, as well as with invasive lobular carcinoma (ILC), which accounts for 10%-15% of all breast cancers. To study the role of E-cadherin in breast oncogenesis, we have introduced conditional E-cadherin mutations into a mouse tumor model based on epithelium-specific knockout of p53. Combined loss of E-cadherin and p53 resulted in accelerated development of invasive and metastatic mammary carcinomas, which show strong resemblance to human ILC. Moreover, loss of E-cadherin induced anoikis resistance and facilitated angiogenesis, thus promoting metastatic disease. Our results suggest that loss of E-cadherin contributes to both mammary tumor initiation and metastasis.
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Loss of E-cadherin is sufficient to promote metastasis of malignant cells in experimental models.
“work with experimental models has demonstrated that loss of E-cadherin is sufficient to promote metastasis of malignant cells”
From Hypoxic control of metastasis (2016) · cites this paper as [66]
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- Authors
- Derksen, P. W. B., Liu, X., Saridin, F., van der Gulden, H., Zevenhoven, J., Evers, B., van Beijnum, J. R., Griffioen, A. W., Vink, J., Krimpenfort, P., Peterse, J. L., Cardiff, R. D., Berns, A., & Jonkers, J.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Maastricht University (NL)
- University of California, Davis (US)
- Corresponding author
- Jonkers, Jos
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 10
- Issue
- 5
- Pages
- 437-449
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2124580184
- Cited by
- 591
- References
- 59
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 19 · 2022: 25 · 2021: 26 · 2020: 23 · 2019: 25 · 2018: 39 · 2017: 36 · 2016: 42 · 2015: 38 · 2014: 39 · 2013: 45 · 2012: 44
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- E-cadherin, p53, invasive lobular carcinoma, breast cancer metastasis, anoikis resistance, angiogenesis, conditional knockout mice, tumor suppressor loss
- MeSH terms
- Animals, Breast Neoplasms, Disease Models, Animal, Female, Humans, Mice, Inbred BALB C, Neoplasm Metastasis, Neovascularization, Pathologic, Skin Neoplasms, Tumor Cells, Cultured, Cadherins, Survival Rate, Tumor Suppressor Protein p53, Carcinoma, Lobular, Gene Silencing, Anoikis, Mammary Glands, Human, Mice
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