Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway

Area of Science:

• Cellular and Molecular Biology
• Aging Research
• Cancer Biology

Background:

• Cellular senescence is a crucial mechanism to prevent damaged cell proliferation.
• The regulatory pathways governing senescence remain incompletely understood.
• Integrin beta 3 (ITGB3 or β3) is implicated in cellular processes but its role in senescence is unclear.

Purpose of the Study:

• To investigate the role of integrin beta 3 (β3) in regulating cellular senescence.
• To elucidate the mechanisms by which β3 influences senescence onset and progression.
• To explore the therapeutic potential of targeting β3 in senescence-associated conditions.

Main Methods:

• Investigated the regulation of ITGB3 by the Polycomb protein CBX7.
• Assessed the impact of β3 expression on senescence in human primary fibroblasts.
• Utilized oncogene-induced senescence (OIS) and therapy-induced senescence (TIS) models.
• Examined the effect of the αvβ3 antagonist cilengitide on senescence and SASP.
• Analyzed β3 levels in aging tissues.

Main Results:

• CBX7 regulates β3 expression, which accelerates senescence onset via the TGF-β pathway.
• Downregulation of β3 overrides OIS and TIS, independent of ligand binding.
• Cilengitide blocks the senescence-associated secretory phenotype (SASP) without affecting proliferation.
• Increased β3 levels were observed in aging tissues.

Conclusions:

• Integrin β3 subunit is a novel regulator and marker of cellular senescence.
• Targeting β3 may offer a strategy to modulate the senescence-associated secretory phenotype.
• β3 plays a significant role in both induced and age-related senescence.