RESUMO
The cellular prion protein (PrPC) is a glycoprotein anchored to the cell surface by glycosylphosphatidylinositol (GPI). PrPC is expressed both in the brain and in peripheral tissues. Investigations on PrPC's functions revealed its direct involvement in neurodegenerative and prion diseases, as well as in various physiological processes such as anti-oxidative functions, copper homeostasis, trans-membrane signaling, and cell adhesion. Recent findings have revealed the ectopic expression of PrPC in various cancers including gastric, melanoma, breast, colorectal, pancreatic, as well as rare cancers, where PrPC promotes cellular migration and invasion, tumor growth, and metastasis. Through its downstream signaling, PrPC has also been reported to be involved in resistance to chemotherapy and tumor cell apoptosis. This review summarizes the variance of expression of PrPC in different types of cancers and discusses its roles in their development and progression, as well as its use as a potential target to treat such cancers.
RESUMO
Aging is a biological feature that is characterized by gradual degeneration of function in cells, tissues, organs, or an intact organism due to the accumulation of environmental factors and stresses with time. Several factors have been attributed to aging such as oxidative stress and augmented production or exposure to reactive oxygen species, inflammatory cytokines production, telomere shortening, DNA damage, and, importantly, the deposit of senescent cells. These are irreversibly mitotically inactive, yet metabolically active cells. The reason underlying their senescence lies within the extrinsic and the intrinsic arms. The extrinsic arm is mainly characterized by the expression and the secretory profile known as the senescence-associated secretory phenotype (SASP). The intrinsic arm results from the impact of several genes meant to regulate the cell cycle, such as tumor suppressor genes. P16INK4A is a tumor suppressor and cell cycle regulator that has been linked to aging and senescence. Extensive research has revealed that p16 expression is significantly increased in senescent cells, as well as during natural aging or age-related pathologies. Based on this fact, p16 is considered as a specific biomarker for detecting senescent cells and aging. Other studies have found that p16 is not only a senescence marker, but also a protein with many functions outside of senescence and aging. In this paper, we discuss and shed light on several studies that show the different functions of p16 and provide insights in its role in several biological processes besides senescence and aging.
RESUMO
A plethora of factors have been attributed to underly aging, including oxidative stress, telomere shortening and cellular senescence. Several studies have shown a significant role of the cyclin-dependent kinase inhibitor p16ink4a in senescence and aging. However, its expression in development has been less well documented. Therefore, to further clarify a potential role of p16 in development and aging, we conducted a developmental expression study of p16, as well as of p19ARF and p21, and investigated their expression on the RNA level in brain, heart, liver, and kidney of mice at embryonic, postnatal, adult, and old ages. P16 expression was further assessed on the protein level by immunohistochemistry. Expression of p16 was highly dynamic in all organs in embryonic and postnatal stages and increased dramatically in old mice. Expression of p19 and p21 was less variable and increased to a moderate extent at old age. In addition, we observed a predominant expression of p16 mRNA and protein in liver endothelial cells versus non-endothelial cells of old mice, which suggests a functional role specifically in liver endothelium of old subjects. Thus, p16 dynamic spatiotemporal expression might implicate p16 in developmental and physiological processes in addition to its well-known function in the build-up of senescence.
