IBSP Promotes Breast Cancer Bone Metastasis and Proliferation via BMP-SMAD Signaling Pathway

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-08-08 DOI:10.1002/cnr2.2153

Wei Ding, Di Lv, Mengshen Wang, Dongsheng Pei

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引用次数: 0

Abstract

Background

Integrin-Binding Sialoprotein (IBSP) has been implicated in tumor progression across various cancers. However, the specific role of IBSP in breast cancer remains underexplored. There is a need to investigate the mechanisms by which IBSP influences breast cancer progression and its potential as a therapeutic target.

Aims

This study aims to elucidate the role of IBSP in breast cancer, particularly its impact on tumor progression and its relationship with prognosis. We also seek to understand the underlying mechanisms, including the involvement of the BMP-SMAD signaling pathway, and to explore the potential of targeting IBSP for therapeutic interventions.

Methods and Results

Overexpression of IBSP in breast cancer cells led to increased migration and invasion, whereas IBSP interference reduced these behaviors, indicating its role in enhancing tumor progression. Differentially expressed genes were significantly enriched in the BMP-SMAD signaling pathway, a critical pathway for osteogenic differentiation. Transcription Factor Binding: Dual luciferase reporter assays demonstrated that SMAD4 specifically binds to the IBSP promoter, establishing a regulatory link between SMAD4 and IBSP expression. Silencing IBSP (si-IBSP) mitigated the effects of SMAD4-induced tumor proliferation, confirming that IBSP acts as a downstream target of SMAD4 in the BMP signaling pathway.

Conclusion

Our study reveals that IBSP plays a significant role in breast cancer progression through the BMP-SMAD4 signaling pathway. Targeting IBSP could be a promising therapeutic strategy for breast cancer treatment. Further research into IBSP inhibitors may offer new avenues for improving treatment outcomes and managing breast cancer more effectively.

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IBSP 通过 BMP-SMAD 信号通路促进乳腺癌骨转移和增殖

背景：Integrin-Binding Sialoprotein (IBSP) 与各种癌症的肿瘤进展有关。然而，IBSP 在乳腺癌中的具体作用仍未得到充分探索。目的：本研究旨在阐明 IBSP 在乳腺癌中的作用，尤其是对肿瘤进展的影响及其与预后的关系。我们还试图了解其潜在的机制，包括 BMP-SMAD 信号通路的参与，并探索以 IBSP 为靶点进行治疗干预的潜力：乳腺癌细胞过表达IBSP会导致迁移和侵袭增加，而干扰IBSP则会减少这些行为，这表明IBSP在促进肿瘤进展中的作用。差异表达的基因明显富集于BMP-SMAD信号通路，这是成骨分化的关键通路。转录因子结合：双荧光素酶报告实验表明，SMAD4 与 IBSP 启动子特异性结合，建立了 SMAD4 与 IBSP 表达之间的调控联系。沉默 IBSP（si-IBSP）可减轻 SMAD4 诱导的肿瘤增殖的影响，证实了 IBSP 是 SMAD4 在 BMP 信号通路中的下游靶点：结论：我们的研究揭示了IBSP通过BMP-SMAD4信号通路在乳腺癌进展过程中发挥着重要作用。以 IBSP 为靶点可能是一种很有前景的乳腺癌治疗策略。对 IBSP 抑制剂的进一步研究可能会为改善治疗效果和更有效地控制乳腺癌提供新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.