Verteporfin Suppresses YAP-Induced Glycolysis in Breast Cancer Cells.

IF 2.1 4区 医学 Q2 SURGERY
Journal of Investigative Surgery Pub Date : 2023-12-01 Epub Date: 2023-10-12 DOI:10.1080/08941939.2023.2266732
Hong Chen, Ling-Fei Zhang, Ying Miao, Yun Xi, Xuefei Li, Mo-Fang Liu, Min Zhang, Biao Li
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引用次数: 0

Abstract

Objective: The inhibition of the Hippo pathway through targeting the Yes-associated protein (YAP) presents a novel and promising approach for treating tumors. However, the efficacy of YAP inhibitors in the context of breast cancer (BC) remains incompletely understood. Here, we aimed to investigate the involvement of YAP in BC's metabolic reprogramming and reveal the potential underlying mechanisms. To this end, we assessed the function of verteporfin (VP), a YAP-TEAD complex inhibitor, on the glycolytic activity of BC cells.

Methods: We evaluated the expression of YAP by utilizing immunohistochemistry (IHC) in BC patients who have undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) prior to biopsy/surgery. We employed RNA immunoprecipitation (RIP) and fluorescent in situ hybridization (FISH) assays to assess the interaction between YAP mRNA and human antigen R (HuR) in BC cells. The biological importance of YAP in the metabolism and malignancy of BC was evaluated in vitro. Finally, the effect of VP on glycolysis was determined by using 18F-FDG uptake, glucose consumption, and lactate production assays.

Results: Our studies revealed that high expression of YAP was positively correlated with the maximum uptake value (SUVmax) determined by 18F-FDG PET/CT imaging in BC samples. Inhibition of YAP activity suppressed glycolysis in BC. The mechanism underlying this phenomenon could be the binding of YAP to HuR, which promotes glycolysis in BC cells. Treatment with VP effectively suppressed glycolysis induced by YAP overexpression in BC cells.

Conclusion: VP exhibited anti-glycolytic effect on BC cells, indicating its therapeutic value as an FDA-approved drug.

Verteporfin抑制YAP-诱导的乳腺癌症细胞糖酵解。
目的:通过靶向Yes相关蛋白(YAP)抑制Hippo通路为治疗肿瘤提供了一种新的、有前景的方法。然而,YAP抑制剂在癌症(BC)中的疗效仍不完全清楚。在这里,我们旨在研究YAP在BC代谢重编程中的作用,并揭示潜在的潜在机制。为此,我们评估了维替泊芬(VP),一种YAP-TEAD复合物抑制剂,对BC细胞糖酵解活性的影响。方法:我们利用免疫组织化学(IHC)评估了在活检/手术前接受18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(18F-FDG PET/CT)的BC患者中YAP的表达。我们使用RNA免疫沉淀(RIP)和荧光原位杂交(FISH)分析来评估BC细胞中YAP mRNA和人类抗原R(HuR)之间的相互作用。体外评估YAP在BC代谢和恶性肿瘤中的生物学重要性。最后,通过使用18F-FDG摄取、葡萄糖消耗和乳酸生产测定来确定VP对糖酵解的影响。结果:我们的研究表明,在BC样本中,YAP的高表达与18F-FDG PET/CT成像确定的最大摄取值(SUVmax)呈正相关。YAP活性的抑制抑制了BC的糖酵解。这种现象的潜在机制可能是YAP与HuR的结合,从而促进BC细胞的糖酵解。VP处理有效抑制了由YAP过表达诱导的BC细胞糖酵解。结论:VP对BC细胞具有抗糖酵解作用,表明其作为美国食品药品监督管理局批准的药物具有治疗价值。
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
CiteScore
4.20
自引率
0.00%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Journal of Investigative Surgery publishes peer-reviewed scientific articles for the advancement of surgery, to the ultimate benefit of patient care and rehabilitation. It is the only journal that encompasses the individual and collaborative efforts of scientists in human and veterinary medicine, dentistry, basic and applied sciences, engineering, and law and ethics. The journal is dedicated to the publication of outstanding articles of interest to the surgical research community.
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