层粘连蛋白的生物力学特性及其对癌症进展的影响
Biomechanical properties of laminins and their impact on cancer progression
影响因子:8.30000
分区:医学2区 Top / 生化与分子生物学2区 生物物理2区 肿瘤学2区
发表日期:2024 Nov
作者:
Elena Nonnast, Emilia Mira, Santos Mañes
摘要
层粘连蛋白（LMS）构成了形成基底膜（BM）必不可少的异三聚糖蛋白家族。它们充当细胞和细胞外基质（ECM）之间的分子桥，从而传递影响细胞行为和组织组织的信号。在癌症病理学领域，LMS调节关键过程，例如迁移，分化或纤维化。这篇综述批判性地研究了LMS对肿瘤进展的多方面影响，特别关注同工型特异性结构功能关系，以及这种结构多样性如何促进BMS的生物力学特性。 LM与整联蛋白和非整合蛋白细胞表面受体以及其他ECM蛋白的相互作用改变了癌细胞对ECM刚度的反应，最终影响了恶性细胞违反BM的能力，这是转移性传播的限制性步骤。理解LM驱动的肿瘤生物力学基础机制具有更好地了解癌症病理学的潜力，并设计了新的靶向治疗策略。
Abstract
Laminins (LMs) constitute a family of heterotrimeric glycoproteins essential for the formation of basement membranes (BM). They act as molecular bridges between cells and the extracellular matrix (ECM), thereby transmitting signals influencing cell behavior and tissue organization. In the realm of cancer pathobiology, LMs regulate key processes such as migration, differentiation, or fibrosis. This review critically examines the multifaceted impact of LMs on tumor progression, with a particular focus on the isoform-specific structure-function relationships, and how this structural diversity contributes to the biomechanical properties of BMs. LM interactions with integrin and non-integrin cell surface receptors, as well as with other ECM proteins, modify the response of cancer cells to the ECM stiffness, ultimately influencing the capacity of malignant cells to breach the BM, a limiting step in metastatic dissemination. Comprehension of the mechanisms underlying LM-driven tumor biomechanics holds potential for better understand cancer pathobiology and design new targeted therapeutic strategies.