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IMP3 promotes stem-like properties in triple-negative breast cancer by regulating SLUG
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Journal Article
IMP3 promotes stem-like properties in triple-negative breast cancer by regulating SLUG
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38
/ 45
/ Biomarkers, Tumor - biosynthesis
/ Biomarkers, Tumor - genetics
/ Complications and side effects
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Insulin
/ Medicine
/ Oncology
/ RNA
/ RNA, Messenger - biosynthesis
/ RNA-Binding Proteins - biosynthesis
/ RNA-Binding Proteins - genetics
/ Snail Family Transcription Factors
/ SOXB1 Transcription Factors - genetics
/ Transcription Factors - biosynthesis
/ Transcription Factors - genetics
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - pathology
/ Tumors
