Biomechanical properties of laminins and their impact on cancer progression

Biochim Biophys Acta Rev Cancer. 2024 Nov;1879(6):189181. doi: 10.1016/j.bbcan.2024.189181. Epub 2024 Sep 18.

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.

Keywords: Basement membrane; Laminin; Mechanotransduction; Metastasis; Tissue biomechanics; Vascular niche.

Publication types

  • Review

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Biomechanical Phenomena
  • Disease Progression*
  • Extracellular Matrix* / metabolism
  • Extracellular Matrix* / pathology
  • Humans
  • Laminin* / metabolism
  • Neoplasms* / metabolism
  • Neoplasms* / pathology

Substances

  • Laminin