Elimination of Proliferating Cells Unmasks the Shift from Senescence to Quiescence Caused by Rapamycin. Zoya N. Demidenko

Elimination of Proliferating Cells Unmasks the Shift from Senescence to Quiescence Caused by Rapamycin

Abstract

Background

Depending on cellular context, p53-inducing agents (such as nutlin-3a) cause different outcomes including reversible quiescence and irreversible senescence. Inhibition of mTOR shifts the balance from senescence to quiescence. In cell lines with incomplete responses to p53, this shift may be difficult to document because of a high proportion of proliferating cells contaminating arrested (quiescent and senescent) cells. This problem also complicates the study of senescence caused by minimal levels of p21 that are capable to arrest a few cells.

Methodology

During induction of senescence by low levels of endogenous p53 and ectopic p21, cells were co-treated with nocodazole, which eliminated proliferating cells. As a result, only senescent and quiescent cells remained.

Results and Discussion

This approach revealed that rapamycin efficiently converted nutlin-induced-senescence into quiescence. In the presence of rapamycin, nutlin-arrested MCF-7 cells retained the proliferative potential and small/lean morphology. Using this approach, we also unmasked senescence in cells arrested by low levels of ectopic p21, capable to arrest only a small proportion of HT1080-p21-9 cells. When p21 did cause arrest, mTOR caused senescent phenotype. Rapamycin and high concentrations of nutlin-3a, which inhibit the mTOR pathway in these particular cells, suppressed senescence, ensuring quiescence instead. Thus, p21 causes senescence passively, just by causing arrest, while still active mTOR drives senescent phenotype. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026126

oncotarget journal impact factor Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
https://www.pnas.org/user/logout?current=node/616329


oncotarget impact
When public mention contemporary medicine, precision plays one of the most significant roles and human lives are directly dependent on it. Likewise, any researches related to medicine are required to comply with the top standards. The problem nowadays is that any results of researches can be posted online and used as a reference without being thoroughly verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and decided to develop an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded back in 2010. The key principle of this journal is based on Altmetric scores that are used as a quality indicator. That allows both readers and authors to verify publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with respective scores higher than 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the required assistance to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This article was published back in 2018 by Oncotarget and completed by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hereby, the publication about melanoma, was used for citations in different news articles 69 times. Moreover, it was mentioned in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This study has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get useful scientific facts. Oncotarget is glad to have the ability to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
https://medicalxpress.com/journals/oncotarget/

Comments

Post a Comment

Popular posts from this blog

Oncotarget. Zoya N. Demidenko

Image
Oncotarget .  Zoya N. Demidenko  Welcome to oncotarget.net, a website about  Oncotarget , a peer-reviewed open access research journal focusing on all topics surrounding cancer research. Oncotarget is published by Impact Journals of Orchard Park, New York. Impact Journals meets the standards established Wellcome Trust Publisher Requirements and is included on the Wellcome Trust List of Compliant Publishers.  Oncotarget is proud to have multiple Nobel Prize winning members on its editorial board, in addition to editors who have won the Lasker Prize and other prestigious recognitions. The open-access model employed by Oncotarget allows for free dissemination of thoroughly vetted peer-reviewed research material to the general public, leading to bigger and more frequent scientific breakthroughs. Because of Oncotarget’s uniquely varied scope, the journal has consistently published research on a wide range of subject areas, allowing readers to access an unparalleled diversity of knowledge in
Read more

Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets.

Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets. ABSTRACT Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1
Read more

Hypoxia suppresses conversion from proliferative arrest to cellular senescence. Zoya N Demidenko

Hypoxia suppresses conversion from proliferative arrest to cellular senescence Abstract Unlike reversible quiescence, cellular senescence is characterized by a large flat cell morphology, β-gal staining and irreversible loss of regenerative (i.e., replicative) potential. Conversion from proliferative arrest to irreversible senescence, a process named geroconversion, is driven in part by growth-promoting pathways such as mammalian target of rapamycin (mTOR). During cell cycle arrest, mTOR converts reversible arrest into senescence. Inhibitors of mTOR can suppress geroconversion, maintaining quiescence instead. It was shown that hypoxia inhibits mTOR. Therefore, we suggest that hypoxia may suppress geroconversion. Here we tested this hypothesis. In HT-p21-9 cells, expression of inducible p21 caused cell cycle arrest without inhibiting mTOR, leading to senescence. Hypoxia did not prevent p21 induction and proliferative arrest, but instead inhibited the mTOR pathway and geroconversion. Exp
Read more