Farnesyltransferase Inhibitor (R115777) Targets CENPF to Inhibit Breast Cancer Bone Metastasis by Regulating the PI3k/AKT/mTOR/PTHrP Pathway.

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2025-07-10 DOI:10.1016/j.clbc.2025.07.002

Jialong Liu, Jingbo Sun, Hongquan Fang, Junjie Luo, Mee Phangphongphanh, Yang Zou, Yiyi Jin, Xinyi Tao, Kun Zhou, Yunyao Deng, Lixin Liu, Gang Xiao, Ninglei Li, Xiaolong Liu

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引用次数: 0

Abstract

Background: Farnesyltransferase inhibitor R115777 has shown promising antitumor effects in various types of cancer by targeting RAS proteins and CENPF farnesylation. To explore its potential in breast cancer (BC), In our study, we aimed to uncover its specific efficacy and underlying mechanisms.

Methods: Through knockdown experiments, we observed that inhibiting CENPF effectively suppressed the growth and metastasis of BC cells, both in vitro and in vivo.

Results: Remarkably, R115777 displayed a selective affinity for CENPF, leading to the inhibition of its-mediated proliferation and bone metastasis in BC cells. Further investigation unveiled that this inhibitory effect was linked to the activation of the PI3K-AKT-mTOR signaling pathway by R115777. Consequently, the secretion of parathyroid hormone-related peptide (PTHrP), a factor crucial for bone marrow development, was detected and inhibited by R115777. As a result, this cascade of events significantly impeded bone metastasis in BC.

Conclusion: Our findings highlight the potential of R115777 as a novel therapeutic strategy for preventing bone metastasis in breast cancer. By specifically targeting CENPF and modulating the PI3K-AKT-mTORC1 pathway, R115777 emerges as a promising targeted treatment option in combating the progression and metastasis of breast cancer.

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Farnesyltransferase Inhibitor （R115777）通过调控PI3k/AKT/mTOR/PTHrP通路靶向CENPF抑制乳腺癌骨转移

背景：法尼基转移酶抑制剂R115777通过靶向RAS蛋白和CENPF法尼基化，在多种类型的癌症中显示出良好的抗肿瘤作用。在我们的研究中，我们旨在揭示其特定的疗效和潜在的机制。方法：通过敲低实验，在体外和体内均观察到抑制CENPF可有效抑制BC细胞的生长和转移。结果：值得注意的是，R115777对CENPF表现出选择性亲和力，导致其介导的BC细胞增殖和骨转移受到抑制。进一步的研究表明，这种抑制作用与R115777激活PI3K-AKT-mTOR信号通路有关。因此，R115777检测并抑制了骨髓发育关键因子甲状旁腺激素相关肽（PTHrP）的分泌。结果，这一连串的事件显著地阻碍了BC的骨转移。结论：我们的研究结果强调了R115777作为一种预防乳腺癌骨转移的新治疗策略的潜力。通过特异性靶向CENPF并调节PI3K-AKT-mTORC1通路，R115777成为对抗乳腺癌进展和转移的有希望的靶向治疗选择。

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

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.