title: Transient SNAIL1 expression is necessary for metastatic competence in breast cancer.
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.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Hung D
authors.initials: HD
authors.lastname: Tran
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Krishna
authors.initials: K
authors.lastname: Luitel
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. ICCE Institute, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. ICCE Institute, Washington University School of Medicine, St. Louis, Missouri. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri dtran@dom.wustl.edu glongmor@dom.wustl.edu.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri dtran@dom.wustl.edu glongmor@dom.wustl.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Tran
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors