靶向癌症中的磷酸肌醇信号传导:研究脂质的相关技术和治疗干预的新途径。
Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.
发表日期:2023
作者:
Alicia Llorente, Ryan M Loughran, Brooke M Emerling
来源:
BIOSENSORS & BIOELECTRONICS
摘要:
磷酸肌醇在许多生物活动中发挥重要作用,对整体细胞功能至关重要。由于其复杂的化学结构、定位和低丰度,磷酸肌醇领域当前的挑战包括准确测量和识别特定变体,特别是具有酰基链的变体。研究人员正在大力开发创新技术和方法来应对这些挑战,并加深我们对磷酸肌醇信号传导对细胞生物学影响的理解。本文概述了磷酸肌醇研究的最新进展,包括质谱、脂质生物传感器和使用荧光传感器的实时活性测定。事实证明,这些方法有助于全面探索磷酸肌醇的细胞分布和动力学,并揭示了这些脂质在人类健康和包括癌症在内的各种病理过程中日益增长的重要性。为了说明磷酸肌醇信号传导在疾病中的重要性,这一观点还强调了名为磷脂酰肌醇 5-磷酸 4-激酶 (PI5P4Ks) 的脂质激酶家族的作用,该家族最近已成为令人兴奋的癌症治疗靶点。对磷酸肌醇信号传导的持续探索不仅加深了我们对细胞生物学的理解,而且为癌症治疗的新干预措施带来了希望。版权所有 © 2023 Llorente、Loughran 和 Emerling。
Phosphoinositides serve as essential players in numerous biological activities and are critical for overall cellular function. Due to their complex chemical structures, localization, and low abundance, current challenges in the phosphoinositide field include the accurate measurement and identification of specific variants, particularly those with acyl chains. Researchers are intensively developing innovative techniques and approaches to address these challenges and advance our understanding of the impact of phosphoinositide signaling on cellular biology. This article provides an overview of recent advances in the study of phosphoinositides, including mass spectrometry, lipid biosensors, and real-time activity assays using fluorometric sensors. These methodologies have proven instrumental for a comprehensive exploration of the cellular distribution and dynamics of phosphoinositides and have shed light on the growing significance of these lipids in human health and various pathological processes, including cancer. To illustrate the importance of phosphoinositide signaling in disease, this perspective also highlights the role of a family of lipid kinases named phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks), which have recently emerged as exciting therapeutic targets for cancer treatment. The ongoing exploration of phosphoinositide signaling not only deepens our understanding of cellular biology but also holds promise for novel interventions in cancer therapy.Copyright © 2023 Llorente, Loughran and Emerling.