p16 INK4a , and p14 ARF Expressions in Carcinogenesis of Squamous Cell Carcinoma of the Lip

Akatlı, Ayşe Nur; Ayva, Ebru Sebnem; Bozdoğan, Önder

doi:10.51847/vezzdfupif

Cited by 1 publication

(1 citation statement)

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“…Studies using murine models have highlighted the high prevalence of senescent cells in pre-malignant tumors, thus explaining the slow growth and low malignancy of these tumors [135]. In this model, senescence was associated with the activation of tumor suppressor proteins, such as p53, p16 INK4A , and ARF, and their loss or inactivation led to tumor-malignant progression [136][137][138]. Furthermore, system cells rapidly eliminate senescent tumor cells, resulting in efficient tumor regression [135,139].…”

Section: Oxidative Stress and Senescencementioning

confidence: 99%

Cutaneous Redox Senescence

Sarandy,

Gonçalves,

Valacchi

2024

Biomedicines

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Our current understanding of skin cell senescence involves the role of environmental stressors (UV, O3, cigarette smoke, particulate matter, etc.), lifestyle (diet, exercise, etc.) as well as genetic factors (metabolic changes, hormonal, etc.). The common mechanism of action of these stressors is the disturbance of cellular redox balance characterized by increased free radicals and reactive oxygen species (ROS), and when these overload the intrinsic antioxidant defense system, it can lead to an oxidative stress cellular condition. The main redox mechanisms that activate cellular senescence in the skin involve (1) the oxidative damage of telomeres causing their shortening; (2) the oxidation of proteomes and DNA damage; (3) an a in lysosomal mass through the increased activity of resident enzymes such as senescence-associated β-galactosidase (SA-β-gal) as well as other proteins that are products of lysosomal activity; (4) and the increased expression of SASP, in particular pro-inflammatory cytokines transcriptionally regulated by NF-κB. However, the main targets of ROS on the skin are the proteome (oxi-proteome), followed by telomeres, nucleic acids (DNAs), lipids, proteins, and cytoplasmic organelles. As a result, cell cycle arrest pathways, lipid peroxidation, increased lysosomal content and dysfunctional mitochondria, and SASP synthesis occur. Furthermore, oxidative stress in skin cells increases the activity of p16INK4A and p53 as inhibitors of Rb and CDks, which are important for maintaining the cell cycle. p53 also promotes the inactivation of mTOR-mediated autophagic and apoptotic pathways, leading to senescence. However, these markers alone cannot establish the state of cellular senescence, and multiple analyses are encouraged for confirmation. An updated and more comprehensive approach to investigating skin senescence should include further assays of ox-inflammatory molecular pathways that can consolidate the understanding of cutaneous redox senescence.

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