An overview of extracellular matrix and its remodeling in the development of cancer and metastasis with a glance at therapeutic approaches

Abstract

The extracellular matrix (ECM) is an inevitable part of tissues able to provide structural support for cells depending on the purpose of tissues and organs. The dynamic characteristics of ECM let this system fluently interact with the extrinsic triggers and get stiffed, remodeled, and/or degraded ending in maintaining tissue homeostasis. ECM could serve as the platform for cancer progression. The dysregulation of biochemical and biomechanical ECM features might take participate in some pathological conditions such as aging, tissue destruction, fibrosis, and particularly cancer. Tumors can reprogram how ECM remodels by producing factors able to induce protein synthesis, matrix proteinase expression, degradation of the basement membrane, growth signals and proliferation, angiogenesis, and metastasis. Therefore, targeting the ECM components, their secretion, and their interactions with other cells or tumors could be a promising strategy in cancer therapies. The present study initially introduces the physiological functions of ECM and then discusses how tumor‐dependent dysregulation of ECM could facilitate cancer progression and ends with reviewing the novel therapeutic strategies regarding ECM.

Substrate O‐glycosylation actively regulates extracellular proteolysis

“…), which initiates a sequence of molecular cascades essential for preserving a dynamically regulated extracellular environment (Kollet et al, 2024 ; Vidak et al, 2019 ). Therefore, precise regulation of the activity of the proteases is critical, given that dysregulation of proteolytic activities can underlie different pathological conditions, including inflammatory disorders and cancer (Afshar et al, 2023 ; Park et al, 2020 ).…”