IMP3 promotes stem-like properties in triple-negative breast cancer by regulating SLUG
Authors
Samanta, SanjoySun, Huayan
Goel, Hira Lal
Pursell, Bryan M.
Chang, C.
Khan, A.
Greiner, Dale L.
Cao, S.
Lim, E.
Shultz, Leonard D.
Mercurio, Arthur M.
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Pathology
Department of Molecular, Cell and Cancer Biology
Document Type
Journal ArticlePublication Date
2015-05-18Keywords
Cancer Biology
Metadata
Show full item recordAbstract
IMP3 (insulin-like growth factor-2 mRNA binding protein 3) is an oncofetal protein whose expression is prognostic for poor outcome in several cancers. Although IMP3 is expressed preferentially in triple-negative breast cancer (TNBC), its function is poorly understood. We observed that IMP3 expression is significantly higher in tumor initiating than in non-tumor initiating breast cancer cells and we demonstrate that IMP3 contributes to self-renewal and tumor initiation, properties associated with cancer stem cells (CSCs). The mechanism by which IMP3 contributes to this phenotype involves its ability to induce the stem cell factor SOX2. IMP3 does not interact with SOX2 mRNA significantly or regulate SOX2 expression directly. We discovered that IMP3 binds avidly to SNAI2 (SLUG) mRNA and regulates its expression by binding to the 5' UTR. This finding is significant because SLUG has been implicated in breast CSCs and TNBC. Moreover, we show that SOX2 is a transcriptional target of SLUG. These data establish a novel mechanism of breast tumor initiation involving IMP3 and they provide a rationale for its association with aggressive disease and poor outcome.Source
Samanta S, Sun H, Goel HL, Pursell B, Chang C, Khan A, Greiner DL, Cao S, Lim E, Shultz LD, Mercurio AM. IMP3 promotes stem-like properties in triple-negative breast cancer by regulating SLUG. Oncogene. 2015 May 18. doi: 10.1038/onc.2015.164. [Epub ahead of print] PubMed PMID: 25982283.DOI
10.1038/onc.2015.164Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36529PubMed ID
25982283Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/onc.2015.164