Laboratory of Immunology and Biology of Metastasis, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, 40126, Italy.
IRCCS Azienda Ospedaliera Universitaria di Bologna, Bologna, 40138, Italy.
Cell Commun Signal. 2024 Oct 11;22(1):489. doi: 10.1186/s12964-024-01876-4.
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.
脂质筏是富含胆固醇和鞘脂的动态微区，通过组织和浓缩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、筏相关小窝和人类表皮生长因子受体之间的相互作用在癌症生物学中具有重要意义，特别是在乳腺癌和胃癌治疗耐药性方面。本综述探讨了脂质筏的结构和功能特征，它们在 EGFR 和 HER2 信号中的参与，以及脂质筏/CXCL12/CXCR4/HER2 轴对骨转移的影响。我们还讨论了靶向脂质筏和 caveolin-1 以增强针对 HER2 阳性癌症的治疗策略的潜力，以及曲妥珠单抗或抗体药物偶联物与 caveolin-1 共定位对治疗反应的影响。新出现的证据表明，通过几种策略，包括降低胆固醇的分子，破坏脂质筏的完整性或沉默 caveolin-1，可以影响 HER2 的可用性和内化，增强针对 HER2 的靶向治疗，并提供一种新的方法来对抗耐药性并提高治疗效果。
