Targeting RSK2 enhances the efficacy of IGF1R inhibitor against triple-negative breast cancer via antagonizing IGF1/IGF1R signaling mediated by GATA3-IGFBP5 pathway.
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OpenAlex 토픽 ·
Growth Hormone and Insulin-like Growth Factors
Metastasis and carcinoma case studies
Cancer, Hypoxia, and Metabolism
Targeting the IGF1 system holds promise as a therapeutic approach for breast cancer.
APA
Tian-jiao Shan, Lei Li, et al. (2026). Targeting RSK2 enhances the efficacy of IGF1R inhibitor against triple-negative breast cancer via antagonizing IGF1/IGF1R signaling mediated by GATA3-IGFBP5 pathway.. Acta pharmacologica Sinica, 47(5), 1300-1311. https://doi.org/10.1038/s41401-025-01673-w
MLA
Tian-jiao Shan, et al.. "Targeting RSK2 enhances the efficacy of IGF1R inhibitor against triple-negative breast cancer via antagonizing IGF1/IGF1R signaling mediated by GATA3-IGFBP5 pathway.." Acta pharmacologica Sinica, vol. 47, no. 5, 2026, pp. 1300-1311.
PMID
41501418 ↗
Abstract 한글 요약
Targeting the IGF1 system holds promise as a therapeutic approach for breast cancer. However, the intricate nature of IGF1 signaling and suboptimal drug combinations have resulted in limited clinical success. This study demonstrates that silencing p90 ribosomal S6 kinase 2 (RSK2), a downstream effector of the Ras/ERK pathway, inhibits IGF1 signaling by upregulating the expression and secretion of IGFBP5, a potent inhibitor of the IGF1-IGF1R axis that competes with IGF1 for binding. Mechanistically, GATA3 is identified as a novel transcription factor for IGFBP5, and RSK2 promotes GATA3 degradation by directly binding and phosphorylating it at serine 308, thus suppressing IGFBP5 transcription. Moreover, combined treatment with the RSK2 inhibitor LJH685 and the IGF1R inhibitor PPP significantly reduces metastasis of triple-negative breast cancer (TNBC) in both in vitro and in vivo models. These findings uncover new targets for synergistic antitumor therapy in TNBC and suggest that concurrent inhibition of IGF1R and RSK2 may offer an effective combinatorial treatment strategy.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Ribosomal Protein S6 Kinases
- 90-kDa
- Triple Negative Breast Neoplasms
- Humans
- Female
- Animals
- Signal Transduction
- Receptor
- IGF Type 1
- Insulin-Like Growth Factor I
- GATA3 Transcription Factor
- Cell Line
- Tumor
- Mice
- Nude
- Antineoplastic Agents
- Inbred BALB C
- Receptors
- Somatomedin
- Xenograft Model Antitumor Assays
- GATA3
- IGF1
- IGFBP5
- RSK2
… 외 1개
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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