scholarly journals Temporal inhibition of autophagy reveals segmental reversal of aging with increased cancer risk

2019 ◽  
Author(s):  
Liam D Cassidy ◽  
Andrew RJ Young ◽  
Christopher NJ Young ◽  
Elizabeth J Soilleux ◽  
Edward Fielder ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Complete Recovery ◽  
Degradation Pathway ◽  
Tumor Formation ◽  
Aging Effects ◽  
Significant Extension ◽  
Basic Quality ◽  
Autophagy Inhibition ◽  
Temporal Inhibition

AbstractAutophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to aging. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the aging process, and whether autophagy restoration can counteract these aging effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan, however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumor formation. Thus our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumor suppressive and oncogenic, sequentially.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

Role of the mitogenic property and kinase activity of p60src in tumor formation by Rous sarcoma virus.

1984 ◽  
Vol 49 (2) ◽  
pp. 325-332 ◽  
Author(s):  
F Poirier ◽  
P Jullien ◽  
P Dezelee ◽  
G Dambrine ◽  
E Esnault ◽  
...  
Keyword(s):  
Rous Sarcoma Virus ◽  
Kinase Activity ◽  
Tumor Formation ◽  
Rous Sarcoma ◽  
Sarcoma Virus

scholarly journals YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lan Jin ◽  
Yunhe Chen ◽  
Dan Cheng ◽  
Zhikai He ◽  
Xinyi Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Transcriptional Coactivator ◽  
Inhibitory Protein ◽  
Potential Therapeutic Target ◽  
Related Cell ◽  
Autophagy Inhibition

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

scholarly journals Strategies and cognitive reserve to preserve lexical production in aging

GeroScience ◽  
2021 ◽  
Author(s):  
Monica Baciu ◽  
Sonja Banjac ◽  
Elise Roger ◽  
Célise Haldin ◽  
Marcela Perrone-Bertolotti ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Individual Variability ◽  
Future Research ◽  
Aging Effects ◽  
Main Hypothesis ◽  
Compensatory Strategies ◽  
Age Related ◽  
Complementary Domain

AbstractIn the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

scholarly journals Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

2021 ◽  
Vol 22 (14) ◽  
pp. 7249
Author(s):  
Siyer Roohani ◽  
Frank Tacke
Keyword(s):  
Bone Marrow ◽  
Liver Injury ◽  
Current Knowledge ◽  
Hepatocellular Cancer ◽  
Complete Recovery ◽  
Hepatic Macrophages ◽  
Liver Injuries ◽  
Microbial Products ◽  
Injured Liver

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.

scholarly journals DIAPH2, PTPRD and HIC1 Gene Polymorphisms and Laryngeal Cancer Risk

2021 ◽  
Vol 18 (14) ◽  
pp. 7486
Author(s):  
Mirosław Śnit ◽  
Maciej Misiołek ◽  
Wojciech Ścierski ◽  
Anna Koniewska ◽  
Grażyna Stryjewska-Makuch ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Laryngeal Cancer ◽  
Basic Research ◽  
Control Groups ◽  
Allele Distribution ◽  
Study Results ◽  
Risk Patients ◽  
And Control ◽  
The Relationship

AIM, DIAPH2, PTPRD and HIC1 are the cell glycoprotein, which play an important role in the occurrence and development of tumors. This study was designed to assess the association between DIAPH2, PTPRD and HIC1 SNPs and laryngeal cancer risk. PATIENTS AND METHODS: This study including 267 patients with histologically confirmed laryngeal cancer and 157 controls. The relationship between genetic variations DIAPH2 (rs6620138), PTPRD (rs3765142) and HIC1 (rs9901806) and the onset of laryngeal cancer were investigated. Statistical analysis to calculate the relationship between DIAPH2, PTPRD and HIC1 genes polymorphism and pathogenesis of laryngeal cancer. RESULTS: The results showed that rs6620138 DIAPH2 polymorphism could increase the onset risk of laryngeal cancer. Statistically significant differences in allele distribution of rs6620138 DIAPH2 and rs9901806 HIC1 in the case and control groups subgroups. CONCLUSIONS: This study results suggested that genetic variation of rs6620138 DIAPH2 polymorphism is related to the susceptibility to laryngeal cancer. Our results provide a basis to begin basic research on the role of DIAPH2 gene in the pathogenesis of laryngeal cancer.

scholarly journals Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3183
Author(s):  
Edward R. Sauter ◽  
Brandy Heckman-Stoddard
Keyword(s):  
Weight Loss ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Dramatic Improvement ◽  
Role Of Government ◽  
Sustained Weight Loss ◽  
Historical Role ◽  
Cancer Risk Reduction

Metabolic (bariatric) surgery (MBS) is recommended for individuals with a BMI > 40 kg/m2 or those with a BMI 35–40 kg/m2 who have one or more obesity related comorbidities. MBS leads to greater initial and sustained weight loss than nonsurgical weight loss approaches. MBS provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus and cardiovascular risk. While the number of MBS procedures performed in the U.S. and worldwide continues to increase, they are still only performed on one percent of the affected population. MBS also appears to reduce the risk of certain obesity related cancers, although which cancers are favorably impacted vary by study, who benefits most is uncertain, and the mechanism(s) driving this risk reduction are mostly speculative. The goal of this manuscript is to highlight 1) emerging evidence that MBS influences cancer risk, and that the potential benefit appears to vary based on cancer, gender, surgical procedure, and likely other variables; 2) the role of the NIH in MBS research in T2DM and CV risk for many years, and more recently in cancer; and 3) the opportunity for research to understand the mechanism(s) by which MBS influences cancer. There is evidence that women benefit more from MBS than men, that MBS may actually increase the risk of colorectal cancer in both women and men, and there is speculation that the benefit in cancer risk reduction may vary according to which MBS procedure an individual undergoes. Herein, we review what is currently known, the historical role of government, especially the National Institutes of Health (NIH), in driving this research, and provide suggestions that we believe could lead to a better understanding of whether and how MBS impacts cancer risk, which cancers are impacted either favorably or unfavorably, the role of the NIH and other research agencies, and key questions to address that will help us to move the science forward.

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

Sign in / Sign up

Export Citation Format

Share Document