The transcriptional repressor Snail promotes mammary tumor recurrence.
Breast cancer recurrence is a fundamental clinical manifestation of tumor progression and represents the principal cause of death from this disease. Using a conditional transgenic mouse model for the recurrence of HER2/neu-induced mammary tumors, we demonstrate that the transcriptional repressor Snail is spontaneously upregulated in recurrent tumors in vivo and that recurrence is accompanied by epithelial-to-mesenchymal transition (EMT). Consistent with a causal role for Snail in these processes, we show that Snail is sufficient to induce EMT in primary tumor cells, that Snail is sufficient to promote mammary tumor recurrence in vivo, and that high levels of Snail predict decreased relapse-free survival in women with breast cancer. In aggregate, our observations strongly implicate Snail in the process of breast cancer recurrence.
Moody
Susan E
SE
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Perez
Denise
D
Pan
Tien-chi
TC
Sarkisian
Christopher J
CJ
Portocarrero
Carla P
CP
Sterner
Christopher J
CJ
Notorfrancesco
Kathleen L
KL
Cardiff
Robert D
RD
Chodosh
Lewis A
LA
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018719:Erb-b2 Receptor Tyrosine Kinases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors