However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. In contrast to this, there is a growing body of evidence Senescence and aging: the critical roles of p53 | Oncogene Abnormal oncogenic signaling early in tumor progression initially promotes proliferation but eventually triggers a cellular senescence program. (2006). The utility of senescence has, thus, remained inconclusive. Most tumors show evidence of infiltrating immune and inflammatory cells, and chronic inflammatory disorders are known to increase the overall risk of cancer development. Cellular Senescence and Anti-Cancer Therapy The DNA damage response (DDR) has a central role in cellular senescence. As part of this, the expression of CXCR2 and its ligands (such as IL-8 or GRO) are up-regulated, contributing to reinforce growth arrest. Role The role of senescence in cancer is highly controversial. senescence In senescence growth arrest, two core senescence-regulating pathways, p53 and p16 INK4a /Rb, play a critical role. It is estimated by the year 2030, 2.2 billion people around the world will be overweight and 1.1 billion people will be obese. Beyond cellular senescence, these observations illuminate a novel role for STING-mediated autophagy as an additional barrier against early neoplastic progression in normal cells. Our study helps explain a major paradox in the senescence field: How activated oncogenes induce senescence but at the same time predispose cells to transformation through BRCA1 pathway. Pitt researchers to contribute to building an atlas of cellular senescence. Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Molecular Cell Article Paradoxical Role for Wild-Type p53 multiple hallmarks of senescence, yet the cells remain highly invasive and retain the ability to grow out as distant metastases lines from the Cancer Cell Line Encyclopedia (Barretina et al., 2012) taking expression data from only wild-type p53 samples. The apparently paradoxical tumor-suppressive role of Stat3 in liver cancer is in accordance with cumulative findings in other tumor types. cellular senescence #truthPeep Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC. On the contrary note, cellular senescence has an ability for tumor promotion, which is presumably related to senescence-associated secretory phenotype (SASP) factors. CELLULAR SENESCENCE: OVERVIEW. Cellular senescence. The Paradoxical Role of Cellular Senescence in Cancer Cellular senescence is a highly durable mode of cell cycle arrest that occurs in aged or DNA-damaged cells. A growing number of studies have convincingly demonstrated a paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. The importance of cellular senescence as a tumour suppressor is further demonstrated by cell fusion experiments [ 12] that provide evidence that growth arrest observed in senescent cells has a strong influence over the growth in proliferating cells and cellular oncogenes of tumour cells. Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. SASP can be induced in both cancer and normal cells by stress, oncogenes, or therapy (therapy induced senescence) (69, 70). Moreover, abundant evidence suggests that senescence plays an important role in aging. Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. In this review, we discuss the current state of the field with a focus on the paradoxical outcomes of the senescence-induced inflammatory responses in the context of cancer. The tumor-suppressive function of Abstract. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. 1,14 Senescent cells secrete many factors into the extracellular environment, which is known as a senescence-associated secretory phenotype (SASP). Furthermore, our studies revealed FOXO1 as a critical cofactor and determinant for the regulation of PR hormone sensitivity. However, ROS/RNS can also induce cellular senescence, apoptosis and, in this capacity, are anti-tumourigenic. As aforementioned, ROS or, more accurately, ROS-mediated damage have been extensively implicated in the induction of cellular senescence and in the onset of aging disorders. Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage. Telomeres, the extremities of linear chromosomes, perform an essential role in implementing these proliferative boundaries and preventing the propagation of potentially cancerous cells. Cellular senescence and the associated secretory phenotype (SASP) promote disease in the aged population. Cellular senescence - its role in cancer and the response to ionizing radiation. 49,75,109,151 The definition of an oncogene is a gene that actively promotes tumorigenesis. We propose a model whereby the NPMc+ pro-senescence activity needs to be evaded for oncogenic transformation, even though NPMc+ can concomitantly blunt the Arf/p53 pathway. Genome Integr 2011; 2:7. Hence it is logical to propose the role of crocodile gut microbiome in contributing to its health and resilience. Cancer Cell Metabolism. In ovarian cancer cells, PR-A is relatively insensitive to hormone, and PR-B (but not PR-A) is capable of inducing FOXO1 and p21 expression required for progestin-mediated cellular senescence in ovarian cancer cells. Title:Cellular Senescence and Anti-Cancer Therapy VOLUME: 20 ISSUE: 7 Author(s):Jieqiong You, Rong Dong, Meidan Ying, Qiaojun He, Ji Cao * and Bo Yang* Affiliation:Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Cellular senescence refers to the essentially irreversible arrest of cell proliferation (growth) that occurs when cells experience potentially oncogenic stress (Figure 1).The permanence of the senescence growth arrest enforces the idea that the senescence response evolved at least in part to suppress the development of cancer (). The paradoxical role of senescence as a protective mechanism against the eradication of cancer might be detrimental to the possible contribution of senescence to aging. We propose a model whereby the NPMc+ pro-senescence activity needs to be evaded for oncogenic transformation, even though NPMc+ can concomitantly blunt the Arf/p53 pathway. Longevity, cellular senescence and the gut microbiome: Lessons to be learned from crocodiles @article{Siddiqui2021LongevityCS, title={Longevity, cellular senescence and the gut microbiome: Lessons to be learned from crocodiles}, author={Ruqaiyyah Siddiqui and Sutherland K. Maciver There are different types of ROS/RNS, which have variable in vivo half-lives and reactivity. Although SASP from senescent cells can kill neighboring normal cells, the apoptosis-resistance of senescent cells protects those cells from SASP. [13] Contents 1Causes 2Pathology 3Benefits 4History 5See also 6References Causes[edit] The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. senescence; SASP; stem cells Cellular senescence is widely considered an archetypal mecha-nism of tumor suppression. Clinical and epidemiological data have associated chronic inflammation with cancer progression. Normal human fibroblasts enter a state of irreversible growth arrest after a finite number of cell divisions in vitro caused by telomere shortening but cancer cells appear to bypass this replicative limit and proliferate indefinitely.Recent reports have shown that cellular senescence can also be induced prematurely by a number of cellular stresses such as [Show full abstract] paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. Europe PMC is an archive of life sciences journal literature. Herein we describe the crocodile gut microbiome composition, in relation to crocodile longevity and cellular senescence, the genome and epigenome as well as the resistance of crocodiles to infectious diseases and cancer. Sappan heartwood (Caesalpinia sappan L.) have been known to have cytotoxicity effect toward several cancer cells.This research was conducted to develop Caesalpinia sappan L. heartwood ethanolic extract (CSE) as chemopreventive agent which can be used as From the evolutionary point of view, senescence is predictable The androgen receptor (AR) plays a leading role in the control of prostate cancer (PCa) growth. On the other hand, inflammatory factors produced by senescent cells contribute to the promotion of tumour growth. As with many of the previously described roles for senescence, the type of inflammation established by the senescence phenotype is varied and dependent on context. Surprisingly, however, we find that NPMc+ induces cellular senescence and that E1A is able to overcome this response. Diabetes and obesity are the main risk factors for the development of the metabolic syndrome and in the liver of non The molecular regulation of senescence in cancer and aging is discussed. DOI: 10.1016/j.heliyon.2021.e08594 Corpus ID: 245160908. Both autophagy and senescence can allow cancer cells to mitigate or perhaps delay the damage incurred by clinical therapeutic modalities, escape cell death and prolong survival. Introduction. Nature Cell Biology, in press. Highly and uncontrolled cell proliferation on cancer cells may boost ROS level intracellular accumulation up significantly. By contrast, the SASP does not depend on either p53 or p16 INK4a, which suggests the existence of an independent senescence regulatory network that controls the SASP.Having observed high levels of induction of microRNA miR-146a during 11,13,14 However, the role of CSIG in cancer development and progression has not been studied widely. Chronic liver disease has globally risen mainly due to a prevalent hepatitis C virus (HCV) infection rate and an epidemic of obesity. Decades of study on cell cycle regulation have provided great insight into human cellular life span barriers, as well as their dysregulation during tumorigenesis. The sudden p53 induction in sarcomas and hepatocellular carcinomas provokes senescence followed by tumor elimination. Telomeres, the extremities of linear chromosomes, perform an essential role in implementing these proliferative boundaries and preventing the propagation of potentially cancerous cells. The tumour suppressor p53, a stress-responsive transcription factor, plays a central role in cellular senescence. However, research from several groups over the past two decades has convincingly demonstrated a paradoxical role for senescence emanating from its Paradoxical suppression of cellular senescence by p53. Most cells throughout the body can divide and multiply to replace old Moreover, abundant evidence suggests that senescence plays an important role in aging. Cellular senescence is a state in which normal healthy cells do not have the ability to divide. Title:Cellular Senescence and Anti-Cancer Therapy VOLUME: 20 ISSUE: 7 Author(s):Jieqiong You, Rong Dong, Meidan Ying, Qiaojun He, Ji Cao * and Bo Yang* Affiliation:Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Senescence, the state of irreversible cell-cycle arrest, plays paradoxical albeit important roles in vivo: it protects organisms against cancer but also contributes to age-related loss of tissue function. Recent data suggest that the prolonged presence of senescent cells, and especially the SASP, could be deleterious, Paradoxical roles of cellular senescence in cancer Cellular senescence is a normal biological stress response that blocks cell cycle progression to limit the propagation of damaged, potentially pre-malignant cells. In the original article in the first sentence of Introduction , Paragraph 1 there were incorrect citations of Collado et al., 2007 and Loaiza and Demaria, 2016. This article will attempt to briefly explore the mechanistic insights of cellular senescence in cancer cells and assess its feasibility as a clinical strategy or endpoint in oncological control. In cancer senescence has a paradoxical role. Moreover, because cancer is a disease that results from mutations, it would seem illogical to conceive of a cancer therapy that is based on increasing the mutation burden of a cancer cell. Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage. PC3, but not DU145, human prostate cancer cells retain the coregulators required While immune cells are often observed in early hyperplastic lesions in vivo, there remains debate over whether these However, at what tumor stage and how Ned David is the co-founder of Unity Biotechnology, a company developing senolytic medicinesmolecules that target and destroy senescent cells in the human body.In this episode, Ned explains the science of cellular senescence and how it impacts the aging process. .Accessed on November 9 Researcher Francis Rodier figured out for the very first time cellular senescence was occurring this means that the cells were starting to stop aging and dividing. It is known that, in lab specimens, clearing senescent cells from Surprisingly, however, we find that NPMc+ induces cellular senescence and that E1A is able to overcome this response. In glioblastoma, deficiency of the phosphatase and tensin homolog tumor suppressor (PTEN) led to astrocyte malignant transformation upon Stat3 inhibition, arguing for an antioncogenic function of Stat3. Among them, kinase modulators have been a primary focus for use in cancer treatment. Here we demonstrate that p53-induced quiescence actually results [CANCER RESEARCH 63, 27052715, June 1, 2003] Review Tumor Cell Senescence in Cancer Treatment1 Igor B. Roninson2 Department of Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607-7170 Abstract senescence should not be viewed as merely an end point in a cells life cycle but rather as a physiological state determined by the homeostatic Cell The molecular regulation of senescence in cancer and aging is discussed. This corrects the article "The Paradoxical Role of Cellular Senescence in Cancer", 722205. Increasing evidence suggests that CSIG plays important roles in many physiological and pathophysiological processes including cell senescence, nucleolar stress response, and UV-induced apoptosis. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Together these mechanisms limit excessive or aberrant cellular proliferation, and so the state of senescence protects against the development of cancer. Nevertheless, there is emerging evidence that responses to checkpoint immunotherapies can be enhanced by increasing the mutation load of the cancer. Cellular senescence is Research in cancer cell metabolism focuses on altered cellular metabolic pathways that support the cancer phenotype, which is characterized by unchecked cell proliferation, resistance to metabolic and oxidative stress, ability to evade programmed cell death, reduced dependence on growth factor signals, insensitivity to growth p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. There is mounting evidence that cellular senescence acts as a cancer brake because it takes many divisions to accumulate all the changes needed to become a cancer cell. Not only does it contribute to the irreversible loss of replicative In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. Role of cellular senescence in aging and cancer [27:00]; History of senescence in scientific study [40:30]; The cellular senescence paradox [46:00]; Developing medicines that target cellular senescence [52:15]; Neds lessons on risk analysis in business [1:05:15]; The search for a molecule that could eliminate senescent cells [1:15:15]; 1. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic This was causing serious damage to the These cellular states have been considered tumor suppression mechanisms. Corrigendum: The Paradoxical Role of Cellular Senescence in Cancer Jing Yang, Jing Yang, Mengmeng Liu, Mengmeng Liu, Dongchun Hong, Dongchun Hong, Musheng Zeng, Xing Zhang; Affiliations Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China CXCR2 signaling, senescence, and cancer. Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Interestingly, structurally different AR antagonists with distinct mechanisms of antagonism induce cell senescence, a mechanism that inhibits cell cycle progression, and thus seems to be a key cellular response for the treatment of PCa. Role of Telomerase in Malignant Transformation. RESULTS/ANTICIPATED RESULTS: CKM con- Role of ER calcium in beta cell senescence and diabetes sisting of combination IFN-? phenotype observed in cancer cells that arise due to oncogenic stress or treatment with therapeutic agents. Initially, SASP is Decades of study on cell cycle regulation have provided great insight into human cellular life span barriers, as well as their dysregulation during tumorigenesis. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress Cellular senescence was formerly described by Hayflick and colleagues, after witnessing that normal diploid cells in culture had a limited number of cell divisions and entered a permanent cell cycle arrest (Hayflick and Moorhead, 1961).Hayflick observed that the nondividing cells remained viable for many weeks and suggested that this proliferative halt and finite lifetime In ovarian cancer cells, PR-A is relatively insensitive to hormone, and PR-B (but not PR-A) is capable of inducing FOXO1 and p21 expression required for progestin-mediated cellular senescence in ovarian cancer cells. The paradoxical role of senescence as a protective mechanism against the eradication of cancer might be detrimental to the possible contribution of senescence to aging. ScienceDaily. Overall, the potential of cellular senescence to be used as a target for anticancer therapy is a close reality in the clinical practice. Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. The multifaceted nature of cellular senescence in vivo has been rapidly evolving in recent years, but our understanding of the diverse biological functions of senescent cells remains far from complete. What is becoming clear, however, is that in addition to the well-established mechanism of tumor suppression to protect against unrestricted growth of damaged cells and The paradoxical role of of cancer might be detrimental to the possible contribution of senescence to aging. The seemingly paradoxical effects found in colon cancer are not unique since there is evidence that subsets of human bladder and breast cancers and leukemias can also display increased expression of pRb, and that pRb can protect bladder cancer cells, osteosarcoma cells and hepatic carcinoma cells from apoptosis induced by various agents (44, 47). 5. In this review, we discuss the current state of the field with a focus on the paradoxical outcomes of the senescence-induced inflammatory responses in the context of cancer. A growing number of studies have convincingly demonstrated a paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. The senescence arrest prevents the development of cancer, and the SASP can promote tissue repair. 16 Similarly, SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors. Furthermore, studies have shown that specific ROS/RNS can sensitise cancer cells to ROS-inducing chemotherapy agents. ScienceDaily, 9 November 2021. Cellular senescence was originally identified as a stable exit from the cell cycle caused by the finite proliferative capacity of cultured human fibroblasts (1, 2).Currently, senescence is considered a stress response that can be induced by a wide range of intrinsic and extrinsic insults, including oncogenic activation, oxidative and genotoxic stress, mitochondrial Paradoxically, senescent cells secrete proinflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. //Aasldpubs.Onlinelibrary.Wiley.Com/Doi/10.1002/Hep.24435 '' > Key protein implicated < /a > paradoxical suppression of senescence. 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