Sami Baccouche*, Nejla Fourati, Wissem Siala, Rachid Jlidi and Jamel Daoud
Extracellular Matrices (ECM) serve as the molecular scaffold for cell adhesion, migration, proliferation and differentiation and as a repository of cytokines and molecular cues that determine cell polarization and tissue organization. The EMC alteration conducts to Integrin β3 regroupement, after its TGFβ induced overexpression; important tumorogenesis step that mediates an amplified integrin-Fak-Src signaling leading to aggressive tumor phenotype.
The upstream of these events is the accumulation of stress sensor protein, HIF-1α, which in involved in a constitutive active TGFβ overexpression, epigenetic landscape remodeling and sustaining a Smad2/3 signaling by supressing VHL expression. Together, allowed TGFβ late target genes expression such as: SNAIL, MMP, galectin, paxillin and integrinβ3; and at the same time TGFβ early genes repression such as: p21 and E-cadherin.
This review highlight, subsequent to stress condition (as hypoxia), different feedbacks, whose HIF-1α, TGFβ, ECM alteration and integrin β3 interplay to promote breast cancerogenesis.
Published Date: 2024-01-18; Received Date: 2023-12-14
