Related Experiment Video
Updated: Jul 22, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
IGF2BP3-EGFR-AKT axis promotes breast cancer MDA-MB-231 cell growth
Xintao Jing1, Cong Han2, Qian Li3
1Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University School of Health Science Center, Xi'an 710061, Shaanxi, China; Key Laboratory of Environmentally and Genetically Associated Diseases, Xi'an Jiaotong University School of Health Science Center, Xi'an 710061, Shaanxi, China.
Abstract:
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an emerging prognostic indicator, and its elevated expression correlates with malignancy in a broad spectrum of cancers. However, its regulatory networks have not yet been reported. In this study, we identified the regulatory targets of IGF2BP3 in breast cancer MDA-MB-231 cells using RNA immunoprecipitation sequencing (RIP-seq) and high-throughput RNA-sequencing (RNA-seq). We discovered that these targets were enriched in the inflammatory response, endoplasmic reticulum stress, cell cycle, and cancer-related pathways, providing a new perspective for better understanding the functional mechanisms of IGF2BP3. Moreover, we identified that the epidermal growth factor receptor (EGFR), a downstream target, is regulated by IGF2BP3. IGF2BP3 binds to and protects EGFR mRNA from degradation and facilitates cell proliferation via the EGFR/AKT pathway in MDA-MB-231 cells. In addition, IGF2BP3 expression was robust and could not be altered by stimulation with EGF and anti-EGFR siRNA or EGFR signaling pathway inhibitors (gefitinib, LY294002 and SL-327). These results demonstrate that IGF2BP3, as a stubborn oncogene, promotes triple-negative breast cancer MDA-MB-231 cell proliferation by strengthening the role of the EGFR-AKT axis.
Insights
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a key regulator in breast cancer. This study reveals IGF2BP3 strengthens the EGFR-AKT pathway, promoting triple-negative breast cancer cell proliferation.
Area of Science:
- Molecular oncology
- Cancer genomics
Background:
- Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an emerging prognostic indicator associated with malignancy across various cancers.
- The regulatory networks of IGF2BP3, particularly in breast cancer, remain largely uncharacterized.
Purpose of the Study:
- To identify the direct regulatory targets of IGF2BP3 in breast cancer MDA-MB-231 cells.
- To elucidate the functional mechanisms and pathways regulated by IGF2BP3 in cancer progression.
Main Methods:
- RNA immunoprecipitation sequencing (RIP-seq) to identify IGF2BP3-bound RNAs.
- High-throughput RNA sequencing (RNA-seq) to analyze gene expression changes.
- Functional assays to investigate the role of IGF2BP3 in cell proliferation and signaling pathways.
Main Results:
- IGF2BP3 directly binds to and stabilizes epidermal growth factor receptor (EGFR) mRNA, enhancing EGFR expression.
- IGF2BP3 promotes MDA-MB-231 cell proliferation through the EGFR/AKT signaling axis.
- Identified enriched pathways including inflammatory response, endoplasmic reticulum stress, and cell cycle regulation.
Conclusions:
- IGF2BP3 acts as an oncogene in triple-negative breast cancer by stabilizing EGFR mRNA and activating the EGFR/AKT pathway.
- IGF2BP3's role in promoting proliferation is independent of EGFR signaling modulation.
- IGF2BP3 represents a potential therapeutic target for triple-negative breast cancer.
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:16TGF - β Signaling Pathway
01:24Regulation of Angiogenesis and Blood Supply
01:07MAPK Signaling Cascades