Viscoelasticity of extracellular matrix regulate senescence to cancer phenotype.

Abstract

Cellular senescence is a state of irreversible cell cycle arrest and is one of the hallmarks of aging. Accumulation of senescent cells in various tissues and organs of aged individuals contributes to diseases including cancer, diabetes, cardiovascular, osteoporosis. Cancer is one of the negative outcomes of aging process. In vitro senescent and cancer cells both respond to mechanical stimuli. However, underlies molecular mechanism of onset of skin cancer in aged individual is yet unknown. Here, we address this question by studying the senescence to cancer transition on viscoelastic surfaces. We probed the senesce to cancer transition on surface of viscoelastic, elastic, and plastic surfaces. Senescence fibroblast cells on viscoelastic surface formed cluster increased growth and reduced senescent beta gal staining. We found that Senescent cells also exhibited reduced spread area compared to elastic and plastic surface. Transition of senescent cells to cancer lead by the cross talk between mtor signaling pathway and protein kinase c beta. In conclusion our study shows that change in viscoelastic property of microenvironment cause the accumulated senescent to transform to cancer phenotype.