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IGFBP3 Promotes Mammary Stem Cells Activity and Tumorigenesis by Regulating IGF Bioavailability

GSE290400 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/07/01 Platform GPL24676Platform GPL19057
Summary
Mammary stem cells (MaSCs) play important roles in mammary gland homeostasis. A better understanding of MaSC activity enhances our knowledge of breast cancer initiation and progression, particularly in the context of triple-negative breast cancer (TNBC). Until now, the molecular mechanisms of MaSCs have remained elusive. Our current research has unveiled a significant enrichment of IGFBP3 expression in normal MaSCs, highlighting its indispensable role in maintaining MaSCs stemness and mammary gland development. Moreover, we show that IGFBP3 promotes breast cancer tumorigenesis and progression. Mechanistically, IGFBP3 regulates IGF1/2 bioavailability under the action of MMPs (such as MMP3), activating the IGF1R receptor and its downstream AKT and ERK1/2 signaling pathways. In clinical samples, high expression of either IGFBP3 or MMP3 is associated with poor prognosis in ER-negative or TNBC patients. Future studies should investigate the potential therapeutic benefit of IGFBP3 in TNBC.
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Also filed as BioProject PRJNA1227909 and SRA study SRP566157. Searching any of these in the dataset finder brings you back here.

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