Cellular senescence, one of the hallmarks of cancer, is characterized by cell cycle arrest and the loss of most normal cellular functions while acquiring a hypersecretory, proinflammatory phenotype. The function of senescent cells in cancer cells varies depending on the cellular conditions. Before the occurrence of cancer, senescent cells act as a barrier to prevent its development. But once cancer has occurred, senescent cells play a procancer role. However, few of the current studies have adequately explained the diversity of cellular senescence across cancers. Herein, we concluded the latest intrinsic mechanisms of cellular senescence in detail and emphasized the senescence-associated secretory phenotype as a key contributor to heterogeneity of senescent cells in tumor. We also discussed five kinds of inducers of cellular senescence and the advancement of senolytics in cancer, which are drugs that tend to clear senescent cells. Finally, we summarized the various effects of senescent cells in different cancers and manifested that their functions may be diametrically opposed under different circumstances. In short, this paper contributes to the understanding of the diversity of cellular senescence in cancers and provides novel insight for tumor therapy.
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http://dx.doi.org/10.1002/mco2.695 | DOI Listing |
Cells
January 2025
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases.
View Article and Find Full Text PDFCells
December 2024
Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant stress on tissues and cells, leading to cancer, immune disorders, and a number of diseases. Cellular senescence, the mechanism by which cells counteract stress, prevents cells from unnecessary damage and leads to sustained cell cycle arrest.
View Article and Find Full Text PDFInt J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
View Article and Find Full Text PDFAging Cell
January 2025
Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, China.
The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice.
View Article and Find Full Text PDFHum Cell
January 2025
Department of Nephrology, Zhong Da Hospital, Gulou District, No. 87, Dingjiaqiao, Zhongyangmen Street, Nanjing, 210009, Jiangsu, China.
Autophagy, a cellular degradation process involving the formation and clearance of autophagosomes, is mediated by autophagic proteins, such as microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), and modulated by 3-methyladenine (3-MA) as well as chloroquine (CQ). Senescence, characterised by permanent cell cycle arrest, is marked by proteins such as cyclin-dependent kinase inhibitor 1 (p21) and tumour protein 53 (p53). This study aims to investigate the relationship between cell senescence and renal function in diabetic kidney disease (DKD) and the effect of autophagy on high-glucose-induced cell senescence.
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