scholarly journals Exosomes as Emerging Pro-Tumorigenic Mediators of the Senescence-Associated Secretory Phenotype

2019 ◽  
Vol 20 (10) ◽  
pp. 2547 ◽  
Author(s):  
Rekha Jakhar ◽  
Karen Crasta
Keyword(s):  
Chromosomal Instability ◽  
Cancer Biology ◽  
Biological Function ◽  
Therapeutic Resistance ◽  
Tumor Microenvironments ◽  
Age Related ◽  
Cancer Initiation ◽  
Membrane Bound ◽  
Secretory Phenotype

Communication between cells is quintessential for biological function and cellular homeostasis. Membrane-bound extracellular vesicles known as exosomes play pivotal roles in mediating intercellular communication in tumor microenvironments. These vesicles and exosomes carry and transfer biomolecules such as proteins, lipids and nucleic acids. Here we focus on exosomes secreted from senescent cells. Cellular senescence can alter the microenvironment and influence neighbouring cells via the senescence-associated secretory phenotype (SASP), which consists of factors such as cytokines, chemokines, matrix proteases and growth factors. This review focuses on exosomes as emerging SASP components that can confer pro-tumorigenic effects in pre-malignant recipient cells. This is in addition to their role in carrying SASP factors. Transfer of such exosomal components may potentially lead to cell proliferation, inflammation and chromosomal instability, and consequently cancer initiation. Senescent cells are known to gather in various tissues with age; eliminating senescent cells or blocking the detrimental effects of the SASP has been shown to alleviate multiple age-related phenotypes. Hence, we speculate that a better understanding of the role of exosomes released from senescent cells in the context of cancer biology may have implications for elucidating mechanisms by which aging promotes cancer and other age-related diseases, and how therapeutic resistance is exacerbated with age.

scholarly journals Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1145
Author(s):  
Nesrine Mabrouk ◽  
Silvia Ghione ◽  
Véronique Laurens ◽  
Stéphanie Plenchette ◽  
Ali Bettaieb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Treatment ◽  
Cellular Senescence ◽  
Negative Effects ◽  
No Donors ◽  
Cell State ◽  
Age Related ◽  
A Cell ◽  
Secretory Phenotype

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

Abstract 5577: The role of age-related enhancements of IL-17 in prostate cancer initiation and progression

2011 ◽  
Author(s):  
Alejandra De Angulo ◽  
Robert Faris ◽  
David Cavazos ◽  
Christopher Jolly ◽  
Linda A. deGraffenried
Keyword(s):  
Prostate Cancer ◽  
Age Related ◽  
Cancer Initiation

scholarly journals FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sébastien Relier ◽  
Julie Ripoll ◽  
Hélène Guillorit ◽  
Amandine Amalric ◽  
Cyrinne Achour ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Biological Function ◽  
Cancer Management ◽  
Demethylase Activity

AbstractCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N6,2’-O-dimethyladenosine (m6Am) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, fully reverses this phenotype, stressing the role of m6Am modification in stem-like properties acquisition. FTO-mediated regulation of m6Am marking constitutes a reversible pathway controlling CSC abilities. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.

scholarly journals Association of Blood Group Antigen CD59 with Disease

2022 ◽  
pp. 1-12
Author(s):  
Christof Weinstock
Keyword(s):  
Blood Group ◽  
Cell Clone ◽  
Membrane Attack Complex ◽  
Cell Types ◽  
Blood Group Antigen ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Life Threatening ◽  
Membrane Bound

In 2014, the membrane-bound protein CD59 became a blood group antigen. CD59 has been known for decades as an inhibitor of the complement system, located on erythrocytes and on many other cell types. In paroxysmal nocturnal haemoglobinuria (PNH), a stem cell clone with acquired deficiency to express GPI-anchored molecules, including the complement inhibitor CD59, causes severe and life-threatening disease. The lack of CD59, which is the only membrane-bound inhibitor of the membrane attack complex, contributes a major part of the intravascular haemolysis observed in PNH patients. This crucial effect of CD59 in PNH disease prompted studies to investigate its role in other diseases. In this review, the role of CD59 in inflammation, rheumatic disease, and age-related macular degeneration is investigated. Further, the pivotal role of CD59 in PNH and congenital CD59 deficiency is reviewed.

scholarly journals RNAs as Candidate Diagnostic and Prognostic Markers of Prostate Cancer—From Cell Line Models to Liquid Biopsies

Diagnostics ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Marvin Lim ◽  
Anne-Marie Baird ◽  
John Aird ◽  
John Greene ◽  
Dhruv Kapoor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Biology ◽  
Prognostic Markers ◽  
Circular Rna ◽  
Liquid Biopsies ◽  
Non Coding Rna ◽  
Cancer Initiation ◽  
Long Non Coding Rna ◽  
Active Investigation

The treatment landscape of prostate cancer has evolved rapidly over the past five years. The explosion in treatment advances has been witnessed in parallel with significant progress in the field of molecular biomarkers. The advent of next-generation sequencing has enabled the molecular profiling of the genomic and transcriptomic architecture of prostate and other cancers. Coupled with this, is a renewed interest in the role of non-coding RNA (ncRNA) in prostate cancer biology. ncRNA consists of several different classes including small non-coding RNA (sncRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). These families are under active investigation, given their essential roles in cancer initiation, development and progression. This review focuses on the evidence for the role of RNAs in prostate cancer, and their use as diagnostic and prognostic markers, and targets for treatment in this disease.

scholarly journals FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell

2020 ◽  
Author(s):  
Sébastien Relier ◽  
Julie Ripoll ◽  
Hélène Guillorit ◽  
Amandine Amalric ◽  
Florence Boissière ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Biological Function ◽  
Translation Efficiency ◽  
Cancer Management ◽  
Demethylase Activity ◽  
Fine Tune

ABSTRACTCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications dynamic in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its m6Am (N6,2’-O-dimethyladenosine) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, partially reverses this phenotype. FTO-mediated regulation of m6Am marking constitutes a novel, reversible pathway controlling CSC abilities that does not involve transcriptome remodeling, but could fine-tune translation efficiency of selected m6Am marked transcripts. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.

scholarly journals Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini-Review

Gerontology ◽  
2016 ◽  
Vol 62 (5) ◽  
pp. 513-518 ◽  
Author(s):  
Michael C. Velarde ◽  
Marco Demaria
Keyword(s):  
Growth Factors ◽  
Targeted Therapies ◽  
Therapeutic Strategy ◽  
Functional Decline ◽  
Skin Aging ◽  
Negative Effects ◽  
Age Related ◽  
Secretory Phenotype ◽  
Excessive Accumulation

Senescent cells are induced by a wide variety of stimuli. They accumulate in several tissues during aging, including the skin. Senescent cells secrete proinflammatory cytokines, chemokines, growth factors, and proteases, a phenomenon called senescence-associated secretory phenotype (SASP), which are thought to contribute to the functional decline of the skin as a consequence of aging. Due to the potential negative effects of the SASP in aged organisms, drugs that selectively target senescent cells represent an intriguing therapeutic strategy to delay aging and age-related diseases. Here, we review studies on the role of senescent cells in the skin, with particular emphasis on the age-related mechanisms and phenotypes associated with excessive accumulation of cellular senescence. We discuss the aberrant behavior of senescent cells in aging and how the different signaling pathways associated with survival and secretion of senescent cells can be engaged for the development of targeted therapies.

scholarly journals Inhibition of JAK-STAT Signaling Pathway Alleviates Age-Related Phenotypes in Tendon Stem/Progenitor Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Minhao Chen ◽  
Longfei Xiao ◽  
Guangchun Dai ◽  
Panpan Lu ◽  
Yuanwei Zhang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Signaling Pathway ◽  
Critical Role ◽  
Vital Role ◽  
Actin Dynamics ◽  
Tendon Tissue ◽  
Age Related ◽  
Stat Signaling ◽  
Secretory Phenotype

Diminished regeneration or healing capacity of tendon occurs during aging. It has been well demonstrated that tendon stem/progenitor cells (TSPCs) play a vital role in tendon maintenance and repair. Here, we identified an accumulation of senescent TSPCs in tendon tissue with aging. In aged TSPCs, the activity of JAK-STAT signaling pathway was increased. Besides, genetic knockdown of JAK2 or STAT3 significantly attenuated TSPC senescence in aged TSPCs. Pharmacological inhibition of JAK-STAT signaling pathway with AG490 similarly attenuated cellular senescence and senescence-associated secretory phenotype (SASP) of aged TSPCs. In addition, inhibition of JAK-STAT signaling pathway also restored the age-related dysfunctions of TSPCs, including self-renewal, migration, actin dynamics, and stemness. Together, our findings reveal the critical role of JAK-STAT signaling pathway in the regulation of TSPC aging and suggest an ideal therapeutic target for the age-related tendon disorders.

scholarly journals Novel Contributors and Mechanisms of Cellular Senescence in Hypertension-Associated Premature Vascular Aging

2019 ◽  
Vol 32 (8) ◽  
pp. 709-719 ◽  
Author(s):  
Cameron G McCarthy ◽  
Camilla F Wenceslau ◽  
R Clinton Webb ◽  
Bina Joe
Keyword(s):  
Tissue Regeneration ◽  
Cellular Senescence ◽  
Vascular Function ◽  
Growth Arrest ◽  
Matrix Metalloproteases ◽  
Oxygen Species ◽  
Vascular Aging ◽  
Age Related ◽  
Secretory Phenotype

Abstract Hypertension has been described as a condition of premature vascular aging, relative to actual chronological age. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in hypertension. Nonetheless, the precise mechanisms that underlie the aged phenotype of arteries from hypertensive patients and animals remain elusive. Cellular senescence is an age-related physiologic process in which cells undergo irreversible growth arrest. Although controlled senescence negatively regulates cell proliferation and promotes tissue regeneration, uncontrolled senescence can contribute to disease pathogenesis by presenting the senescence-associated secretory phenotype, in which molecules such as proinflammatory cytokines, matrix metalloproteases, and reactive oxygen species are released into tissue microenvironments. This review will address and critically evaluate the current literature on the role of cellular senescence in hypertension, with particular emphasis on cells types that mediate and modulate vascular function and structure.

scholarly journals Autophagy in Tumor Immunity and Viral-Based Immunotherapeutic Approaches in Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2672
Author(s):  
Ali Zahedi-Amiri ◽  
Kyle Malone ◽  
Shawn T. Beug ◽  
Tommy Alain ◽  
Behzad Yeganeh
Keyword(s):  
Recent Progress ◽  
Immune Cell ◽  
Oncolytic Viruses ◽  
Regulatory Mechanisms ◽  
Cancer Therapies ◽  
Management Service ◽  
Tumor Microenvironments ◽  
Cancer Initiation ◽  
Catabolic Process

Autophagy is a fundamental catabolic process essential for the maintenance of cellular and tissue homeostasis, as well as directly contributing to the control of invading pathogens. Unsurprisingly, this process becomes critical in supporting cellular dysregulation that occurs in cancer, particularly the tumor microenvironments and their immune cell infiltration, ultimately playing a role in responses to cancer therapies. Therefore, understanding “cancer autophagy” could help turn this cellular waste-management service into a powerful ally for specific therapeutics. For instance, numerous regulatory mechanisms of the autophagic machinery can contribute to the anti-tumor properties of oncolytic viruses (OVs), which comprise a diverse class of replication-competent viruses with potential as cancer immunotherapeutics. In that context, autophagy can either: promote OV anti-tumor effects by enhancing infectivity and replication, mediating oncolysis, and inducing autophagic and immunogenic cell death; or reduce OV cytotoxicity by providing survival cues to tumor cells. These properties make the catabolic process of autophagy an attractive target for therapeutic combinations looking to enhance the efficacy of OVs. In this article, we review the complicated role of autophagy in cancer initiation and development, its effect on modulating OVs and immunity, and we discuss recent progress and opportunities/challenges in targeting autophagy to enhance oncolytic viral immunotherapy.

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