Transient SNAIL1 expression is necessary for metastatic competence in breast cancer

Hung D. Tran, Krishna Luitel, Michael Kim, Kun Zhang, Gregory D. Longmore, David D. Tran

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a genetic SNAIL1 model by coupling an endogenous SNAIL1 reporter with an inducible SNAIL1 transgene. Using multiple genetic models of breast cancer, we demonstrated that endogenous SNAIL1 expression was restricted to primary tumors that ultimately disseminate. SNAIL1 gene deletion either during the premalignant phase or after primary tumors have reached a palpable size blunted metastasis, indicating that late metastasis was the main driver of metastasis and that this was dependent on SNAIL1. Importantly, SNAIL1 expression during breast cancer metastasis was transient and forced transient, but not continuous. SNAIL1 expression in breast tumors was sufficient to increase metastasis.

Original languageEnglish
Pages (from-to)6330-6340
Number of pages11
JournalCancer research
Volume74
Issue number21
DOIs
StatePublished - Nov 1 2014

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