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Senescence, cancer, autophagy

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https://www.readbyqxmd.com/read/29879550/loss-of-the-ubiquitin-conjugating-enzyme-ube2e3-induces-cellular-senescence
#1
Kendra S Plafker, Katarzyna Zyla, William Berry, Scott M Plafker
Cellular senescence plays essential roles in tissue homeostasis as well as a host of diseases ranging from cancers to age-related neurodegeneration. Various molecular pathways can induce senescence and these different pathways dictate the phenotypic and metabolic changes that accompany the transition to, and maintenance of, the senescence state. Here, we describe a novel senescence phenotype induced by depletion of UBE2E3, a highly-conserved, metazoan ubiquitin conjugating enzyme. Cells depleted of UBE2E3 become senescent in the absence of overt DNA damage and have a distinct senescence-associated secretory phenotype, increased mitochondrial and lysosomal mass, an increased sensitivity to mitochondrial and lysosomal poisons, and an increased basal autophagic flux...
May 21, 2018: Redox Biology
https://www.readbyqxmd.com/read/29805774/p53-and-metabolism-from-mechanism-to-therapeutics
#2
REVIEW
Fernando M Simabuco, Mirian G Morale, Isadora C B Pavan, Ana P Morelli, Fernando R Silva, Rodrigo E Tamura
The tumor cell changes itself and its microenvironment to adapt to different situations, including action of drugs and other agents targeting tumor control. Therefore, metabolism plays an important role in the activation of survival mechanisms to keep the cell proliferative potential. The Warburg effect directs the cellular metabolism towards an aerobic glycolytic pathway, despite the fact that it generates less adenosine triphosphate than oxidative phosphorylation; because it creates the building blocks necessary for cell proliferation...
May 4, 2018: Oncotarget
https://www.readbyqxmd.com/read/29797573/mcl-1-targeting-could-be-an-intriguing-perspective-to-cure-cancer
#3
REVIEW
Anna De Blasio, Renza Vento, Riccardo Di Fiore
The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis...
May 24, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29736310/depletion-of-gamma-glutamylcyclotransferase-in-cancer-cells-induces-autophagy-followed-by-cellular-senescence
#4
Keiko Taniguchi, Kengo Matsumura, Hiromi Ii, Susumu Kageyama, Eishi Ashihara, Tokuhiro Chano, Akihiro Kawauchi, Tatsuhiro Yoshiki, Susumu Nakata
Gamma-glutamylcyclotransferase (GGCT) was originally identified as a protein highly expressed in bladder cancer tissues by proteomic analysis, and its higher expression in a variety of cancers compared to normal tissues have been shown. Depletion of GGCT in various cancer cells results in antiproliferative effects both in vitro and in vivo ; thus it is considered a promising therapeutic target. Although it has been shown that knockdown of GGCT induces cellular senescence and non-apoptotic cell death, associated with upregulation of cyclin-dependent kinase inhibitors (CDKIs) including p21WAF1/CIP1 , the cellular events that follow GGCT depletion are not fully understood...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29696372/roles-of-autophagy-in-controlling-stem-cell-identity-a-perspective-of-self-renewal-and-differentiation
#5
REVIEW
Areechun Sotthibundhu, Wilasinee Promjuntuek, Min Liu, Sanbing Shen, Parinya Noisa
Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs)...
April 25, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29686666/age-and-age-related-diseases-role-of-inflammation-triggers-and-cytokines
#6
REVIEW
Irene Maeve Rea, David S Gibson, Victoria McGilligan, Susan E McNerlan, H Denis Alexander, Owen A Ross
Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#7
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#8
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29608137/mechanisms-and-functions-of-cellular-senescence
#9
Nicolás Herranz, Jesús Gil
Cellular senescence is a highly stable cell cycle arrest that is elicited in response to different stresses. By imposing a growth arrest, senescence limits the replication of old or damaged cells. Besides exiting the cell cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, or autophagy modulation. In addition, senescent cells produce and secrete a complex combination of factors, collectively referred as the senescence-associated secretory phenotype, that mediate most of their non-cell-autonomous effects...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29588413/hydrophobic-patches-on-smad2-and-smad3-determine-selective-binding-to-cofactors
#10
Ken-Ichi Miyazono, Saho Moriwaki, Tomoko Ito, Akira Kurisaki, Makoto Asashima, Masaru Tanokura
The transforming growth factor-β (TGF-β) superfamily of cytokines regulates various biological processes, including cell proliferation, immune responses, autophagy, and senescence. Dysregulation of TGF-β signaling causes various diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription factors involved in TGF-β signaling, and they form heterotrimeric complexes with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in response to TGF-β signaling. These heterotrimeric complexes interact with cofactors to control the expression of TGF-β-dependent genes...
March 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29579719/copper-accumulation-in-senescent-cells-interplay-between-copper-transporters-and-impaired-autophagy
#11
Shashank Masaldan, Sharnel A S Clatworthy, Cristina Gamell, Zoe M Smith, Paul S Francis, Delphine Denoyer, Peter M Meggyesy, Sharon La Fontaine, Michael A Cater
Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro...
June 2018: Redox Biology
https://www.readbyqxmd.com/read/29574749/targeting-egfr-mediated-autophagy-as-a-potential-strategy-for-cancer-therapy
#12
REVIEW
Mopa Alina Sooro, Ni Zhang, Pinghu Zhang
Autophagy is a naturally occurring programed cellular catabolic process stimulated by cellular stress for energy homeostasis maintenance and elimination of harmful substances. It mostly works as pro-survival mechanism but on the other hand deregulation of autophagy has been linked to non-apoptotic cell death known as "type II programed cell death." Emerging evidences indicate that EGFR (epidermal growth factor receptor)-mediated RAS/RAF/MEK/ERK signaling pathway plays a critical role in the induction of autophagy in various tumors...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29574020/sirt1-and-micrornas-the-role-in-breast-lung-and-prostate-cancers
#13
REVIEW
Hedyieh Karbasforooshan, Ali Roohbakhsh, Gholamreza Karimi
Breast cancer and prostate cancer are the most common malignant tumors in female and men, respectively. Furthermore, lung cancer is the leading cause of cancer deaths worldwide. It is an emergency to develop a powerful strategy to treat these threatening cancers more effectively, because of low efficacy and high rates of chemotherapy effects. MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression via induction of translational repression or mRNA degradation. MiRNA deregulation has been linked to cancer initiation and progression...
June 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29562589/an-interplay-between-senescence-apoptosis-and-autophagy-in-glioblastoma-multiforme-role-in-pathogenesis-and-therapeutic-perspective
#14
REVIEW
Elzbieta Pawlowska, Joanna Szczepanska, Magdalena Szatkowska, Janusz Blasiak
Autophagy, cellular senescence, programmed cell death and necrosis are key responses of a cell facing a stress. These effects are partly interconnected, but regulation of their mutual interactions is not completely clear. That regulation seems to be especially important in cancer cells, which have their own program of development and demand more nutrition and energy than normal cells. Glioblastoma multiforme (GBM) belongs to the most aggressive and most difficult to cure cancers, so studies on its pathogenesis and new therapeutic strategies are justified...
March 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518025/emerging-roles-of-p53-family-members-in-glucose-metabolism
#15
REVIEW
Yoko Itahana, Koji Itahana
Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression...
March 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29500364/simultaneous-induction-and-blockade-of-autophagy-by-a-single-agent
#16
Karolina Kucharewicz, Magdalena Dudkowska, Anna Zawadzka, Mikolaj Ogrodnik, Andrzej A Szczepankiewicz, Zbigniew Czarnocki, Ewa Sikora
Besides cell death, autophagy and cell senescence are the main outcomes of anticancer treatment. We demonstrate that tacrine-melatonin heterodimer C10, a potent anti-Alzheimer's disease drug, has an antiproliferative effect on MCF-7 breast cancer cells. The main cell response to a 24 h-treatment with C10 was autophagy enhancement accompanied by inhibition of mTOR and AKT pathways. Significantly increased autophagy markers, such as LC3B- and ATG16L-positive vesicles, confirmed autophagy induction by C10. However, analysis of autophagic flux using mCherry-GFP-LC3B construct revealed inhibition of autophagy by C10 at the late-stage...
March 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29484762/coroglaucigenin-induces-senescence-and-autophagy-in-colorectal-cancer-cells
#17
Yong-Hao Huang, Jing Lei, Guo-Hui Yi, Feng-Ying Huang, Yue-Nan Li, Cai-Chun Wang, Yan Sun, Hao-Fu Dai, Guang-Hong Tan
OBJECTIVES: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood. MATERIALS AND METHODS: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-β-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29435183/expression-and-function-of-nuclear-receptor-coactivator-4-isoforms-in-transformed-endometriotic-and-malignant-ovarian-cells
#18
Stephanie Rockfield, Idhaliz Flores, Meera Nanjundan
Iron is proposed to contribute to the transition from endometriosis to specific subtypes of ovarian cancers (OVCAs). Regulation of intracellular iron occurs via a ferritinophagic process involving NCOA4 (Nuclear Receptor Coactivator 4), represented by two major isoforms (NCOA4α and NCOA4β), whose contribution to ovarian cancer biology remains uninvestigated. We thus generated transformed endometriotic cells (via HRASV12A , c-MYCT58A , and p53 inactivation) whose migratory potential was increased in response to conditioned media from senescent endometriotic cells...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435080/a-novel-approach-to-glioma-therapy-using-an-oncolytic-adenovirus-with-two-specific-promoters
#19
Feng Liu, Kaya Xu, Hua Yang, Yuming Li, Jian Liu, Jixiang Wang, Zhizhong Guan
Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29405784/carvacrol-nanoemulsion-evokes-cell-cycle-arrest-apoptosis-induction-and-autophagy-inhibition-in-doxorubicin-resistant-a549-cell-line
#20
Imran Khan, Ashutosh Bahuguna, Monika Bhardwaj, Tejinder Pal Khaket, Sun Chul Kang
Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549DR ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9...
February 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
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