Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis

Patrick W B Derksen, Xiaoling Liu, Francis Saridin, Hanneke van der Gulden, John Zevenhoven, Bastiaan Evers, Judy R van Beijnum, Arjan W Griffioen, Jacqueline Vink, Paul Krimpenfort, Johannes L Peterse, Robert D Cardiff, Anton Berns, Jos Jonkers

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)437-49
Number of pages13
JournalCancer Cell
Issue number5
Publication statusPublished - Nov 2006

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