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senescence associated secretory phenotype

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https://www.readbyqxmd.com/read/29218300/the-dual-role-of-cellular-senescence-in-developing-tumors-and-their-response-to-cancer-therapy
#1
REVIEW
Markus Schosserer, Johannes Grillari, Michael Breitenbach
Cellular senescence describes an irreversible growth arrest characterized by distinct morphology, gene expression pattern, and secretory phenotype. The final or intermediate stages of senescence can be reached by different genetic mechanisms and in answer to different external and internal stresses. It has been maintained in the literature but never proven by clearcut experiments that the induction of senescence serves the evolutionary purpose of protecting the individual from development and growth of cancers...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29206223/a-model-of-the-onset-of-the-senescence-associated-secretory-phenotype-after-dna-damage-induced-senescence
#2
Patrick Meyer, Pallab Maity, Andre Burkovski, Julian Schwab, Christoph Müssel, Karmveer Singh, Filipa F Ferreira, Linda Krug, Harald J Maier, Meinhard Wlaschek, Thomas Wirth, Hans A Kestler, Karin Scharffetter-Kochanek
Cells and tissues are exposed to stress from numerous sources. Senescence is a protective mechanism that prevents malignant tissue changes and constitutes a fundamental mechanism of aging. It can be accompanied by a senescence associated secretory phenotype (SASP) that causes chronic inflammation. We present a Boolean network model-based gene regulatory network of the SASP, incorporating published gene interaction data. The simulation results describe current biological knowledge. The model predicts different in-silico knockouts that prevent key SASP-mediators, IL-6 and IL-8, from getting activated upon DNA damage...
December 4, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29201428/effect-of-aging-on-the-female-reproductive-function
#3
REVIEW
Koumei Shirasuna, Hisataka Iwata
Aging is a complex biological process that involves the accrual of bodily changes over a long life span. In humans, advanced maternal age is associated with infertility and adverse pregnancy complications. Cellular and organic senescence is hypothesized to contribute to the age-related decline in reproductive function. Accumulating evidence suggests that immune cells play pivotal roles in physiological reproductive function and pregnancy. The concept of "inflammaging" has recently emerged- an age-dependent, low-grade, chronic, and systemic inflammatory state induced by the senescence-associated secretory phenotype (SASP), which is produced by the innate immune, parenchymal, and nonparenchymal cells within the organs...
2017: Contraception and Reproductive Medicine
https://www.readbyqxmd.com/read/29186801/epigenetic-basis-of-cellular-senescence-and-its-implications-in-aging
#4
REVIEW
(no author information available yet)
Cellular senescence is a tumor suppressive response that has become recognized as a major contributor of tissue aging. Senescent cells undergo a stable proliferative arrest that protects against neoplastic transformation, but acquire a secretory phenotype that has long-term deleterious effects. Studies are still unraveling the effector mechanisms that underlie these senescence responses with the goal to identify therapeutic interventions. Such effector mechanisms have been linked to the dramatic remodeling in the epigenetic and chromatin landscape that accompany cellular senescence...
November 24, 2017: Genes
https://www.readbyqxmd.com/read/29184185/cellular-senescence-in-gastrointestinal-diseases-from-pathogenesis-to-therapeutics
#5
REVIEW
Nina Frey, Sascha Venturelli, Lars Zender, Michael Bitzer
Senescence is a durable cell cycle arrest that can be induced in response to various stress factors, such as telomere erosion, DNA damage or the aberrant activation of oncogenes. In addition to its well-established role as a stress response programme, research has revealed important physiological roles of senescence in nondisease settings, such as embryonic development, wound healing, tissue repair and ageing. Senescent cells secrete various cytokines, chemokines, matrix remodelling proteases and growth factors, a phenotype collectively referred to as the senescence-associated secretory phenotype...
November 29, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29182668/extracellular-vesicles-released-by-fibroblasts-undergoing-h-ras-induced-senescence-show-changes-in-lipid-profile
#6
Sandra Buratta, Lorena Urbanelli, Krizia Sagini, Stefano Giovagnoli, Silvia Caponi, Daniele Fioretto, Nico Mitro, Donatella Caruso, Carla Emiliani
Cells release extracellular vesicles (EVs) in their environment and cellular lipids play an important role in their formation, secretion and uptake. Besides, there is also evidence that EV transferred lipids impact on recipient's cell signaling. Cellular senescence is characterized by a state of permanent proliferation arrest and represents a barrier towards the development of neoplastic lesions. A peculiar feature of senescence is the release of many soluble factors, the so-called Senescence-Associated Secretory Phenotype, which play a key role in triggering paracrine senescence signals...
2017: PloS One
https://www.readbyqxmd.com/read/29180744/stem-cell-senescence-drives-age-attenuated-induction-of-pituitary-tumours-in-mouse-models-of-paediatric-craniopharyngioma
#7
Jose Mario Gonzalez-Meljem, Scott Haston, Gabriela Carreno, John R Apps, Sara Pozzi, Christina Stache, Grace Kaushal, Alex Virasami, Leonidas Panousopoulos, Seyedeh Neda Mousavy-Gharavy, Ana Guerrero, Mamunur Rashid, Nital Jani, Colin R Goding, Thomas S Jacques, David J Adams, Jesus Gil, Cynthia L Andoniadou, Juan Pedro Martinez-Barbera
Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis...
November 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174037/cellular-senescence-and-liver-disease-mechanisms-and-therapeutic-strategies
#8
REVIEW
Mei Guo
Cellular senescence is a fundamental cell fate caused by several cellular injuries which results in irreversible cell cycle arrest yet remaining metabolically active across all species. Cellular senescence not only can prevent tumor occurrence by inhibiting the proliferation of injured cells, but also can affect the surrounding cells through the senescence-associated secretory phenotype (SASP). Attractively, accumulating evidence shows that cellular senescence is closely related to various liver diseases. Therapeutic opportunities based on targeting senescent cells and the SASP are considered to be potential strategy for liver diseases...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29161564/cell-biology-when-your-own-chromosomes-act-like-foreign-dna
#9
Alexander Spektor, Neil T Umbreit, David Pellman
Two recent papers report the activation of a pro-inflammatory response by cytoplasmic DNA from aberrant nuclear structures called micronuclei. The findings have implications for tumor immunity, immunotherapy biomarker discovery, and possibly the many-sided effects of senescence-associated secretory phenotype.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29146100/emerging-role-of-extracellular-vesicles-as-a-senescence-associated-secretory-phenotype-insights-into-the-pathophysiology-of-lung-diseases
#10
REVIEW
Tsukasa Kadota, Yu Fujita, Yusuke Yoshioka, Jun Araya, Kazuyoshi Kuwano, Takahiro Ochiya
Aging is a major risk factor for the development of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. A main aspect of aging is the impaired function of maintaining homeostasis in the organs and body, which is associated with cellular senescence. Cellular senescence is recognized as the state of irreversible cell cycle arrest in response to a variety of cellular stresses. Senescent cells are not simply cell cycle-arrested cells; they also affect bystander cells through the secretion of bioactive molecules, termed the senescence-associated secretory phenotype (SASP)...
November 17, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#11
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29133134/sensing-the-breaks-cytosolic-chromatin-in-senescence-and-cancer
#12
Raffaella Di Micco
Cellular senescence constitutes a stable growth arrest characterized by DNA damage response (DDR) activation and by the senescence-associated secretory phenotype (SASP). SASP, through its paracrine effects, stimulates the immune system for senescence eradication. Similarly, chemotherapy-treated cancers activate an interferon-mediated response to induce anti-tumor immunity. Recent studies now uncover a new role for the innate DNA sensing pathway in the recognition of cytosolic chromatin in senescence and cancer...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29089421/genetic-interrogation-of-replicative-senescence-uncovers-a-dual-role-for-usp28-in-coordinating-the-p53-and-gata4-branches-of-the-senescence-program
#13
Anna E Mazzucco, Agata Smogorzewska, Chanhee Kang, Ji Luo, Michael R Schlabach, Qikai Xu, Rupesh Patel, Stephen J Elledge
Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29084133/modulation-of-the-senescence-associated-inflammatory-phenotype-in-human-fibroblasts-by-olive-phenols
#14
Beatrice Menicacci, Caterina Cipriani, Francesca Margheri, Alessandra Mocali, Lisa Giovannelli
Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the "senescence-associated-secretory-phenotype" (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4-6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers...
October 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29074538/tgf-%C3%AE-promotes-genomic-instability-after-loss-of-runx3
#15
Vaidehi Krishnan, Yu Lin Chong, Tuan Zea Tan, Madhura D Kulkarni, Muhammad Bakhait Bin Rahmat, Lavina Sierra Tay, Doorgesh S Jokhun, Amudha Ganesan, Linda Shyue Huey Chuang, Dominic Chih-Cheng Voon, Shivashankar Gv, Jean Paul Thiery, Yoshiaki Ito
Studies of genomic instability have historically focused on intrinsic mechanisms rather than extrinsic mechanisms based on the tumor microenvironment (TME). TGF-β is the most abundantly secreted cytokine in the TME where it imparts various aggressive characteristics including invasive migration, drug resistance and epithelial-to-mesenchymal transition (EMT). Here we show that TGF-β also promotes genomic instability in the form of DNA double strand breaks (DSB) in cancer cells which lack the tumor suppressor gene RUNX3...
October 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29066153/extracellular-matrix-alterations-in-senescent-cells-and-their-significance-in-tissue-homeostasis
#16
REVIEW
Eleni Mavrogonatou, Harris Pratsinis, Adamantia Papadopoulou, Nikos K Karamanos, Dimitris Kletsas
Normal cells after a defined number of successive divisions or after exposure to genotoxic stresses are becoming senescent, characterized by a permanent growth arrest. In addition, they secrete increased levels of pro-inflammatory and catabolic mediators, collectively termed "senescence-associated secretory phenotype". Furthermore, senescent cells exhibit an altered expression and organization of many extracellular matrix components, leading to specific remodeling of their microenvironment. In this review we present the current knowledge on extracellular matrix alterations associated with cellular senescence and critically discuss certain characteristic examples, highlighting the ambiguous role of senescent cells in the homeostasis of various tissues under both normal and pathologic conditions...
October 21, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29053388/some-chemotherapeutics-treated-colon-cancer-cells-display-a-specific-phenotype-being-a-combination-of-stem-like-and-senescent-cell-features
#17
H Was, J Czarnecka, A Kowalczyk, K Barszcz, T Bernas, K Piwocka, B Kaminska
Colorectal cancer (CRC) is the second leading cause of death among cancer patients in the Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, in response to chemotherapy, cancer cells may undergo stress-induced premature senescence (SIPS), which typically results in growth arrest. Nonetheless, these senescent cells were reported to divide in an atypical manner and thus contribute to cancer re-growth. Therefore, we examined if SIPS escape may follow treatment with chemotherapeutics used clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO)...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29052866/runx-mediated-growth-arrest-and-senescence-are-attenuated-by-diverse-mechanisms-in-cells-expressing-runx1-fusion-oncoproteins
#18
Gail Anderson, Nancy Mackay, Kathryn Gilroy, Jodie Hay, Gillian Borland, Alma McDonald, Margaret Bell, Siti Ayuni Hassanudin, Ewan Cameron, James C Neil, Anna Kilbey
RUNX gene over-expression inhibits growth of primary cells but transforms cells with tumor suppressor defects, consistent with reported associations with tumor progression. In contrast, chromosomal translocations involving RUNX1 are detectable in utero, suggesting an initiating role in leukemias. How do cells expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression? Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable to induce senescence-like growth arrest (SLGA) in primary fibroblasts while potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29045001/anti-inflammaging-effects-of-human-alpha-1-antitrypsin
#19
Ye Yuan, Benedetto DiCiaccio, Ying Li, Ahmed S Elshikha, Denis Titov, Brian Brenner, Lee Seifer, Hope Pan, Nurdina Karic, Mohammad A Akbar, Yuanqing Lu, Sihong Song, Lei Zhou
Inflammaging plays an important role in most age-related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha-1 antitrypsin (hAAT) has immune-regulatory, anti-inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti-inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT...
October 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/29044508/differentially-regulated-gene-expression-in-quiescence-vs-senescence-and-identification-of-arid5a-as-a-quiescence-associated-marker
#20
Tarique Anwar, Bijoya Sen, Savera Aggarwal, Rhisita Nath, Ajay Katoch, Mohamed Aiyaz, Nirupma Trehanpati, Sanjeev Khosla, Gayatri Ramakrishna
In multicellular organisms majority of the cells remain in a non-dividing states of either fully differentiated or quiescence (reversible) or senescence (irreversible) conditions. In the present study, gene expression signatures unique to quiescence and senescence were identified using microarray in osteosarcoma cell line, U2OS. Besides, it was also noted that certain genes and pathways like NOD pathway was shared by both the growth arrest conditions. A major highlight of the present study was increased expression of number of chemokines and cytokines in both quiescence and senescence...
October 17, 2017: Journal of Cellular Physiology
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