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Senescence, cancer, autophagy

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https://www.readbyqxmd.com/read/28993779/natural-killer-cell-response-to-chemotherapy-stressed-cancer-cells-role-in-tumor-immunosurveillance
#1
REVIEW
Alessandra Zingoni, Cinzia Fionda, Cristiana Borrelli, Marco Cippitelli, Angela Santoni, Alessandra Soriani
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28990419/proline-metabolism-in-cell-regulation-and-cancer-biology-recent-advances-and-hypotheses
#2
James M Phang
SIGNIFICANCE: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer, but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a P53-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28989041/deciphering-molecular-mechanisms-of-arginine-deiminase-based-therapy-comparative-response-analysis-in-paired-human-primary-and-recurrent-glioblastomas
#3
Claudia Maletzki, Yvonne Rosche, Christin Matzack, Aline Scholz, Doreen William, Carl Friedrich Classen, Bernd Kreikemeyer, Michael Linnebacher, Tomas Fiedler
Arginine auxotrophy constitutes the Achilles' heel for several tumors, among them glioblastoma multiforme (GBM). Hence, arginine-depleting enzymes such as arginine deiminase (ADI) from Streptococcus pyogenes are promising for treatment of primary and maybe even refractory GBM. Based on our previous study in which ADI-susceptibility was shown on a panel of patient-derived GBM cell lines, we here aimed at deciphering underlying molecular mechanisms of ADI-mediated growth inhibition. We found that ADI (35 mU/mL) initially induces a cellular stress-response that is characterized by upregulation of genes primarily belonging to the heat-shock protein family...
October 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28954246/cytoprotective-mechanisms-of-dj-1-against-oxidative-stress-through-modulating-erk1-2-and-ask1-signal-transduction
#4
REVIEW
Stephanie E Oh, M Maral Mouradian
DJ-1 is a highly conserved multifunctional protein linked to both neurodegeneration and neoplasia. Among its various activities is an antioxidant property leading to cytoprotection under oxidative stress conditions. This is associated with the ability to modulate signal transduction events that determine how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy in order to adapt to environmental stimuli and stresses. Alterations in DJ-1 expression or function can disrupt homeostatic signaling networks and initiate cascades that play a role in the pathogenesis of conditions such as Parkinson's disease and cancer...
September 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/28947133/palbociclib-induced-autophagy-and-senescence-in-gastric-cancer-cells
#5
Claudio A Valenzuela, Leandro Vargas, Valentina Martinez, Sindy Bravo, Nelson E Brown
Targeting cyclin D-CDK4/6 kinase complexes has recently been shown to increase the survival of breast cancer patients with estrogen receptor positive breast tumors. Based on these outcomes, CDK4/6 inhibitors are currently being tested, alone o in combination with other drugs, in the treatment of other malignancies characterized by hyper-activation of cyclin D-CDK4/6 complexes. Nonetheless, a better understanding of the cellular processes that are implemented in response to CDK4/6 inhibition is necessary to expand the therapeutic window and confront the development of drug resistance...
September 23, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28923415/diindolylmethane-and-its-halogenated-derivatives-induce-protective-autophagy-in-human-prostate-cancer-cells-via-induction-of-the-oncogenic-protein-aeg-1-and-activation-of-amp-activated-protein-kinase-ampk
#6
Hossam Draz, Alexander A Goldberg, Vladimir I Titorenko, Emma S Tomlinson Guns, Stephen H Safe, J Thomas Sanderson
3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMP-activated protein kinase (AMPK) signaling in prostate cancer cells...
September 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28915623/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#7
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#8
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28877478/the-ulk3-kinase-is-critical-for-convergent-control-of-cancer-associated-fibroblast-activation-by-csl-and-gli
#9
Sandro Goruppi, Maria-Giuseppina Procopio, Seunghee Jo, Andrea Clocchiatti, Victor Neel, G Paolo Dotto
The connection between signaling pathways activating cancer-associated fibroblasts (CAFs) remains to be determined. Metabolic alterations linked to autophagy have also been implicated in CAF activation. CSL/RBPJ, a transcriptional repressor that mediates Notch signaling, suppresses the gene expression program(s), leading to stromal senescence and CAF activation. Deregulated GLI signaling can also contribute to CAF conversion. Here, we report that compromised CSL function depends on GLI activation for conversion of human dermal fibroblasts into CAFs, separately from cellular senescence...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28871086/identification-of-hsp90-inhibitors-as-a-novel-class-of-senolytics
#10
Heike Fuhrmann-Stroissnigg, Yuan Yuan Ling, Jing Zhao, Sara J McGowan, Yi Zhu, Robert W Brooks, Diego Grassi, Siobhan Q Gregg, Jennifer L Stripay, Akaitz Dorronsoro, Lana Corbo, Priscilla Tang, Christina Bukata, Nadja Ring, Mauro Giacca, Xuesen Li, Tamara Tchkonia, James L Kirkland, Laura J Niedernhofer, Paul D Robbins
Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28838537/regulation-of-autophagy-by-mirnas-and-their-emerging-roles-in-tumorigenesis-and-cancer-treatment
#11
Liuxi Chen, Yuxia Zhou, Qiuhua Sun, Jichun Zhou, Hongming Pan, Xinbing Sui
Autophagy is a conserved catabolic process for the degradation and recycling of cytosolic components or organelles through a lysosome-dependent pathway. Autophagy can be induced in response to multiple stress conditions, such as nutrient deprivation, hypoxia, energy depletion, etc. As a result, autophagy can regulate many biological processes, including cell survival, metabolism, differentiation, senescence, and cell death. MicroRNAs (MiRNAs) are small noncoding molecules that regulate gene expression by silencing mRNA targets...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28801249/p53-stability-is-regulated-by-diverse-deubiquitinating-enzymes
#12
REVIEW
Seul-Ki Kwon, Madhuri Saindane, Kwang-Hyun Baek
The tumor suppressor protein p53 has a variety of roles in responses to various stress signals. In such responses, p53 activates specific transcriptional targets that control cell cycle arrest, DNA repair, angiogenesis, autophagy, metabolism, migration, aging, senescence, and apoptosis. Since p53 has been identified as the most frequently altered gene in human cancers, regulation and stabilization of its normal functions are important. Stability of p53 is regulated by the ubiquitin-proteasome pathway (UPP)...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28794999/modulation-of-the-p53-family-network-by-rna-binding-proteins
#13
Chris Lucchesi, Jin Zhang, Xinbin Chen
Since its discovery more than three decades ago, tumor suppressor p53 has been shown to play pivotal roles in both maintaining genomic integrity and tumor suppression. p53 functions as a transcription factor responding to a multitude of cellular stressors, regulating the transcription of many genes involved in cell-cycle arrest, senescence, autophagy, and apoptosis. Extensive work has revealed that p53 is one of the most commonly mutated tumor suppressor genes. The last three decades have demonstrated that p53 activity is controlled through transcriptional regulation and posttranslational modifications...
December 2016: Translational Cancer Research
https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#14
Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673354/the-footprint-of-the-ageing-stroma-in-older-patients-with-breast-cancer
#15
Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers
BACKGROUND: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28671583/natural-compounds-from-herbs-that-can-potentially-execute-as-autophagy-inducers-for-cancer-therapy
#16
REVIEW
Shian-Ren Lin, Yaw-Syan Fu, May-Jywan Tsai, Henrich Cheng, Ching-Feng Weng
Accumulated evidence indicates that autophagy is a response of cancer cells to various anti-cancer therapies. Autophagy is designated as programmed cell death type II, and is characterized by the formation of autophagic vacuoles in the cytoplasm. Numerous herbs, including Chinese herbs, have been applied to cancer treatments as complementary and alternative medicines, supplements, or nutraceuticals to dampen the side or adverse effects of chemotherapy drugs. Moreover, the tumor suppressive actions of herbs and natural products induced autophagy that may lead to cell senescence, increase apoptosis-independent cell death or complement apoptotic processes...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28653662/cdk4-6-and-autophagy-inhibitors-synergistically-induce-senescence-in-rb-positive-cytoplasmic-cyclin-e-negative-cancers
#17
Smruthi Vijayaraghavan, Cansu Karakas, Iman Doostan, Xian Chen, Tuyen Bui, Min Yi, Akshara S Raghavendra, Yang Zhao, Sami I Bashour, Nuhad K Ibrahim, Meghan Karuturi, Jing Wang, Jeffrey D Winkler, Ravi K Amaravadi, Kelly K Hunt, Debu Tripathy, Khandan Keyomarsi
Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack of reliable biomarkers. Here we report that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumours in vivo...
June 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28599295/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#18
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575849/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#19
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#20
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
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