Lipid rafts, caveolae, and epidermal growth factor receptor family: friends or foes?

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2024-10-11 DOI:10.1186/s12964-024-01876-4

Francesca Ruzzi, Chiara Cappello, Maria Sofia Semprini, Laura Scalambra, Stefania Angelicola, Olga Maria Pittino, Lorena Landuzzi, Arianna Palladini, Patrizia Nanni, Pier-Luigi Lollini

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引用次数: 0

Abstract

Lipid rafts are dynamic microdomains enriched with cholesterol and sphingolipids that play critical roles in cellular processes by organizing and concentrating specific proteins involved in signal transduction. The interplay between lipid rafts, raft-associated caveolae and the human epidermal growth factor receptors has significant implications in cancer biology, particularly in breast and gastric cancer therapy resistance. This review examines the structural and functional characteristics of lipid rafts, their involvement in EGFR and HER2 signaling, and the impact of lipid rafts/CXCL12/CXCR4/HER2 axis on bone metastasis. We also discuss the potential of targeting lipid rafts and caveolin-1 to enhance therapeutic strategies against HER2-positive cancers and the impact of co-localization of trastuzumab or antibody drug conjugates with caveolin-1 on therapy response. Emerging evidence suggests that disrupting lipid raft integrity or silencing caveolin-1, through several strategies including cholesterol-lowering molecules, can influence HER2 availability and internalization, enhancing anti-HER2 targeted therapy and offering a novel approach to counteract drug resistance and improve treatment efficacy.

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脂质筏、洞穴和表皮生长因子受体家族：朋友还是敌人？

脂质筏是富含胆固醇和鞘脂的动态微域，通过组织和集中参与信号转导的特定蛋白质，在细胞过程中发挥关键作用。脂质筏、脂质筏相关洞穴和人类表皮生长因子受体之间的相互作用对癌症生物学，尤其是乳腺癌和胃癌的耐药性有重要影响。本综述探讨了脂质筏的结构和功能特征、脂质筏参与表皮生长因子受体和 HER2 信号转导的情况以及脂质筏/CXCL12/CXCR4/HER2 轴对骨转移的影响。我们还讨论了针对脂质筏和洞穴素-1加强HER2阳性癌症治疗策略的潜力，以及曲妥珠单抗或抗体药物共轭物与洞穴素-1共定位对治疗反应的影响。新的证据表明，通过包括降低胆固醇分子在内的多种策略破坏脂质筏完整性或沉默洞穴素-1，可以影响HER2的可用性和内化，从而加强抗HER2靶向治疗，并提供一种对抗耐药性和提高疗效的新方法。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.