层粘连蛋白的生物力学性质及其对癌症进展的影响
Biomechanical properties of laminins and their impact on cancer progression
DOI 原文链接
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影响因子:8.3
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
DOI:
10.1016/j.bbcan.2024.189181
keywords:
Basement membrane; Laminin; Mechanotransduction; Metastasis; Tissue biomechanics; Vascular niche
摘要
层粘连蛋白（Laminins, LMs）是异源三聚体糖蛋白家族的成员，对基底膜（BM）的形成至关重要。它们作为细胞与细胞外基质（ECM）之间的分子桥梁，传递影响细胞行为和组织结构的信号。在癌症病理生物学领域，LMs调控迁移、分化和纤维化等关键过程。本文 critically 检视了 LM 对肿瘤进展的多方面影响，特别关注异构体特异的结构-功能关系，以及这种结构多样性如何影响 BM 的生物力学性质。LM 与整合素和非整合素细胞表面受体的相互作用，以及与其他 ECM 蛋白的结合，改变癌细胞对 ECM 硬度的响应，最终影响恶性细胞突破 BM 的能力，这是转移扩散的限制步骤。理解 LM 驱动的肿瘤生物力学机制，有望更好理解癌症病理生理学，并设计新的靶向治疗策略。
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.