Biomechanical properties of laminins and their impact on cancer progression

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-09-18 DOI:10.1016/j.bbcan.2024.189181
Elena Nonnast, Emilia Mira, Santos Mañes
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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.

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层粘连蛋白的生物力学特性及其对癌症进展的影响
层粘连蛋白(LMs)是形成基底膜(BM)所必需的一种异源三聚糖蛋白。它们是细胞与细胞外基质(ECM)之间的分子桥梁,从而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 可调控迁移、分化或纤维化等关键过程。本综述批判性地研究了 LMs 对肿瘤进展的多方面影响,尤其关注同工酶特异性的结构-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 与整合素和非整合素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 硬度的反应,最终影响了恶性细胞突破 BM 的能力,而这正是转移扩散的限制性步骤。了解 LM 驱动肿瘤生物力学的基本机制有助于更好地理解癌症病理生物学并设计新的靶向治疗策略。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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