scholarly journals Multifaceted roles of SAMHD1 in cancer

2021 ◽  
Author(s):  
Katie-May McLaughlin ◽  
Jindrich Cinatl ◽  
Mark N Wass ◽  
Martin Michaelis
Keyword(s):  
Potential Role ◽  
Tumour Suppressor ◽  
Paediatric Cancer ◽  
Systematic Analysis ◽  
Tumour Suppressor Protein ◽  
Bona Fide ◽  
Cancer Types ◽  
Males And Females ◽  
Cancer Outcome

SAMHD1 is discussed as a tumour suppressor protein, but its potential role in cancer has only been investigated in very few cancer types. Here, we performed a systematic analysis of the TCGA (adult cancer) and TARGET (paediatric cancer) databases, the results of which did not suggest that SAMHD1 should be regarded as a bona fide tumour suppressor. SAMHD1 mutations that interfere with SAMHD1 function were not associated with poor outcome, which would be expected for a tumour suppressor. High SAMHD1 tumour levels were associated with increased survival in some cancer entities and reduced survival in others. Moreover, the data suggested differences in the role of SAMHD1 between males and females and between different races. Often, there was no significant relationship between SAMHD1 levels and cancer outcome. Taken together, our results indicate that SAMHD1 may exert pro- or anti-tumourigenic effects and that SAMHD1 is involved in the oncogenic process in a minority of cancer cases. These findings seem to be in disaccord with a perception and narrative forming in the field suggesting that SAMHD1 is a tumour suppressor. A systematic literature review confirmed that most of the available scientific articles focus on a potential role of SAMHD1 as a tumour suppressor. The reasons for this remain unclear but may include confirmation bias and publication bias. Our findings emphasise that hypotheses, perceptions, and assumptions need to be continuously challenged by using all available data and evidence.

scholarly journals Potential role of acetylsalicilic acid and other non-steroidal anti-inflammatory drugs in cancer risk reduction (literature review)

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
V. V. Buheruk ◽  
O. B. Voloshyna ◽  
L. I. Kovalchuk ◽  
I. V. Balashova ◽  
O. V. Naidionova
Keyword(s):  
Cancer Risk ◽  
Acetylsalicylic Acid ◽  
Potential Role ◽  
Task Force ◽  
Current Systematic Review ◽  
Anti Cancer ◽  
Cancer Types ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.

Long noncoding RNA ANRIL as a novel biomarker in human cancer

2020 ◽  
Vol 16 (35) ◽  
pp. 2981-2995
Author(s):  
Ning Lou ◽  
Guohong Liu ◽  
Yunbao Pan
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Human Cancer ◽  
Cycle Progression ◽  
Diagnosis And Prognosis ◽  
Cancer Types ◽  
Cancer Medicine

The long noncoding RNA ANRIL, located in the human chromosome 9p21 region, has been reported to be involved in tumor progression. ANRIL regulates gene expression via recruiting PRC2 or titrating miRNA; it also participates in signaling pathways. Evidence has indicated that ANRIL is overexpressed in many cancer types and is capable of enhancing cell proliferation and cell cycle progression and inhibiting apoptosis and senescence. ANRIL has the potential to serve as a biomarker for diagnosis and prognosis in cancer. In this article we focus on recent advances in studies of the oncogenic role of ANRIL and its potential role in cancer medicine.

scholarly journals Role for the Related Poly(ADP-Ribose) Polymerases Tankyrase 1 and 2 at Human Telomeres

2002 ◽  
Vol 22 (1) ◽  
pp. 332-342 ◽  
Author(s):  
Brandoch D. Cook ◽  
Jasmin N. Dynek ◽  
William Chang ◽  
Grigoriy Shostak ◽  
Susan Smith
Keyword(s):  
Potential Role ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Continuous Growth ◽  
Telomere Elongation ◽  
Bona Fide ◽  
Tankyrase 1 ◽  
Growth Of Tumor

ABSTRACT Telomere maintenance is essential for the continuous growth of tumor cells. In most human tumors telomeres are maintained by telomerase, a specialized reverse transcriptase. Tankyrase 1, a human telomeric poly(ADP-ribose) polymerase (PARP), positively regulates telomere length through its interaction with TRF1, a telomeric DNA-binding protein. Tankyrase 1 ADP-ribosylates TRF1, inhibiting its binding to telomeric DNA. Overexpression of tankyrase 1 in the nucleus promotes telomere elongation, suggesting that tankyrase 1 regulates access of telomerase to the telomeric complex. The recent identification of a closely related homolog of tankyrase 1, tankyrase 2, opens the possibility for a second PARP at telomeres. We therefore sought to establish the role of tankyrase 1 at telomeres and to determine if tankyrase 2 might have a telomeric function. We show that endogenous tankyrase 1 is a component of the human telomeric complex. We demonstrate that telomere elongation by tankyrase 1 requires the catalytic activity of the PARP domain and does not occur in telomerase-negative primary human cells. To investigate a potential role for tankyrase 2 at telomeres, recombinant tankyrase 2 was subjected to an in vitro PARP assay. Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres. These findings establish tankyrase 2 as a bona fide PARP, with itself and TRF1 as acceptors of ADP-ribosylation, and suggest the possibility of a role for tankyrase 2 at telomeres.

Role of ESCRT component HD-PTP/PTPN23 in cancer

2017 ◽  
Vol 45 (3) ◽  
pp. 845-854 ◽  
Author(s):  
Marie-Claude Gingras ◽  
Jalal M. Kazan ◽  
Arnim Pause
Keyword(s):  
Plasma Membrane ◽  
Cancer Susceptibility ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Surface Receptors ◽  
Endosomal Sorting ◽  
Bona Fide

Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. However, the bona fide role of ESCRT components in tumorigenesis has not been clearly demonstrated. The ESCRT member HD-PTP/PTPN23 was recently identified as a novel haplo-insufficient tumour suppressor in vitro and in vivo, in mice and humans. In this mini-review, we outline the role of the ESCRT components in cancer and summarize the functions of HD-PTP/PTPN23 in tumorigenesis.

scholarly journals Cell-autonomous role of TGFβ and IL-2 receptors in CD4+ and CD8+ inducible regulatory T-cell generation during GVHD

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5575-5583 ◽  
Author(s):  
Norifumi Sawamukai ◽  
Atsushi Satake ◽  
Amanda M. Schmidt ◽  
Ian T. Lamborn ◽  
Priti Ojha ◽  
...  
Keyword(s):  
T Cells ◽  
Potential Role ◽  
Acute Gvhd ◽  
De Novo ◽  
Receptor Expression ◽  
Tgfβ Receptor ◽  
Bona Fide ◽  
Deficient Mice ◽  
Transplantation Recipient

Abstract FoxP3+ regulatory T cells (Tregs) suppress GVHD while preserving graft-versus-tumor effects, making them an attractive target for GVHD therapy. The donor-derived Treg pool can potentially be derived from the expansion of preexisting natural Tregs (nTregs) or from de novo generation of inducible Tregs (iTregs) from donor Tconvs in the transplantation recipient. Using an MHC-mismatched model of acute GVHD, in the present study we found that the Treg pool was comprised equally of donor-derived nTregs and iTregs. Experiments using various combinations of T cells from wild-type and FoxP3-deficient mice suggested that both preexisting donor nTregs and the generation of iTregs in the recipient mice contribute to protection against GVHD. Surprisingly, CD8+FoxP3+ T cells represented approximately 70% of the iTreg pool. These CD8+FoxP3+ T cells shared phenotypic markers with their CD4+ counterparts and displayed suppressive activity, suggesting that they were bona fide iTregs. Both CD4+ and CD8+ Tregs appeared to be protective against GVHD-induced lethality and required IL-2 and TGFβ receptor expression for their generation. These data illustrate the complex makeup of the donor-derived FoxP3+ Treg pool in allogeneic recipients and their potential role in protection against GVHD.

scholarly journals Cancer and Tumour Suppressor p53 Encounters at the Juncture of Sex Disparity

2021 ◽  
Vol 12 ◽  
Author(s):  
Sue Haupt ◽  
Ygal Haupt
Keyword(s):  
Tumour Suppressor ◽  
Redox Activity ◽  
Epigenetic Alterations ◽  
Chief Operating Officer ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Sex Disparities ◽  
Males And Females ◽  
Sex Disparity ◽  
Tumour Suppressor P53

There are many differences in cancer manifestation between men and women. New understanding of the origin of these point to fundamental distinctions in the genetic code and its demise. Tumour suppressor protein p53 is the chief operating officer of cancer defence and critically acts to safeguard against sustained DNA damaged. P53 cannot be ignored in cancer sex disparity. In this review we discuss the greater prevalence and associated death rates for non-reproductive cancers in males. The major tumour suppressor protein p53, encoded in the TP53 gene is our chosen context. It is fitting to ask why somatic TP53 mutation incidence is estimated to be disproportionately higher among males in the population for these types of cancers compared with females? We scrutinised the literature for evidence of predisposing genetic and epigenetic alterations that may explain this sex bias. Our second approach was to explore whether redox activity, either externally imposed or inherent to males and females, may define distinct risks that could contribute to the clear cancer sex disparities.

Commentary on “A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?” (Johnson et al., 2009)

2009 ◽  
Vol 4 (6) ◽  
pp. 615-621 ◽  
Author(s):  
Ian W. Craig ◽  
Claire M.A. Haworth ◽  
Robert Plomin
Keyword(s):  
X Chromosome ◽  
Potential Role ◽  
Gene Action ◽  
General Intelligence ◽  
Compelling Evidence ◽  
Linked Gene ◽  
Buffering Effect ◽  
Chromosomal Genes ◽  
Males And Females

Johnson et al.'s (2009) article highlights the role of X-chromosomal genes in general intelligence and draws attention to their potential role in explaining the observed greater variance for this trait in males and their excess at both extremes of the distribution. We note that this would result from a simple additive effect of X-linked intelligence genes and also discuss the potentially important contribution of recessive deleterious loci. The buffering effect of heterozygosity in females will be partly constrained by the skewing of X-inactivation patterns increasing the variance of females beyond what is expected. Furthermore, escape of some X-linked genes from in-activation may also be relevant to male—female variance comparisons. We also comment on the difficulty of establishing the extent to which the X chromosome is enriched for intelligence genes and point out that their estimates of the proportion of genes influencing general intelligence that might be located on the X chromosome rely on some doubtful premises, especially concerning the likely equivalence of X-linked gene action in males and females. Finally, we discuss the increasingly compelling evidence for the accumulation of genes on the X chromosome that have selective benefit to males, including those implicated infertility and some manifestations of intelligence.

The role of the Wilms' tumour-suppressor protein WT1 in apoptosis

2008 ◽  
Vol 36 (4) ◽  
pp. 629-631 ◽  
Author(s):  
Jörg Hartkamp ◽  
Stefan G.E. Roberts
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Wilms Tumour ◽  
Zinc Finger Transcription Factor ◽  
Tumour Suppressor Protein ◽  
Proliferation And Apoptosis

The Wilms' tumour-suppressor gene (WT1), encodes a zinc-finger transcription factor that is critical for the development of several organs, including the kidneys, gonads and spleen. Despite its identification as a tumour suppressor that plays a crucial role in the formation of a paediatric malignancy of the kidneys (Wilms' tumour), it has also emerged as an oncogenic factor influencing proliferation and apoptosis in a large variety of adult cancers. This review focuses on new insights into WT1's role in early development and its potential oncogenic role in adult cancer.

Transcriptional regulation by the Wilms' tumour suppressor protein WT1

2004 ◽  
Vol 32 (6) ◽  
pp. 932-935 ◽  
Author(s):  
K.J. Wagner ◽  
S.G.E. Roberts
Keyword(s):  
Transcriptional Activation ◽  
Solid Tumour ◽  
Small Region ◽  
Tumour Suppressor ◽  
Wilms Tumour ◽  
Transcriptional Activation Domain ◽  
Tumour Suppressor Protein ◽  
Context Specific ◽  
Specific Control

Wilms' tumour is a paediatric malignancy of the kidneys and is the most common solid tumour found in children. The Wilms' tumour suppressor protein WT1 is mutated in approx. 15% of Wilms' tumours, and is aberrantly expressed in many others. WT1 can manifest both tumour suppressor and oncogenic activities, but the reasons for this are not yet clear. The Wilms' tumour suppressor protein WT1 is a transcriptional activator, the function of which is under cell-context-specific control. We have previously described a small region at the N-terminus of WT1 (suppression domain) that inhibits the transcriptional activation domain by contacting a co-suppressor protein. We recently identified BASP1 as one of the components of the co-suppressor. Here, we analyse the mechanism of action of the WT1 suppression domain, and discuss its function in the context of the role of WT1 as a regulator of development.

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