Investigating an Evolutionarily Conserved Role for the Tousled-like Kinase in Genome Stability and as a Novel Target for the Treatment of Ovarian Cancer

2013 ◽  
Author(s):  
Jill M. Schumacher
Keyword(s):  
Ovarian Cancer ◽  
Genome Stability ◽  
Evolutionarily Conserved ◽  
Novel Target

scholarly journals Transporter Associated with Antigen Processing 1 (TAP1) as a Potential Biomarker for Breast, Lung, Liver and Ovarian Cancer using Health Informatics

2020 ◽  
Author(s):  
Anika Tabassum ◽  
Md. Nazmus Samdani ◽  
Tarak Chandra Dhali ◽  
Rahat Alam ◽  
Foysal Ahammad ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Health Informatics ◽  
Antigen Processing ◽  
Multi Drug Resistance ◽  
P Value ◽  
Mhc I ◽  
Transporter Protein ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
Novel Target

Transporter associated with antigen processing 1 (TAP1) gene codes for a transporter protein, which is responsible for tumor antigen presentation in the MHC I or HLA complex. A defect in the gene results in an inadequate tumor tracking. TAP1 may also influence multi drug resistance, which is an extreme threat in providing treatment by drugs which are chemotherapeutic. The gene of TAP1 was analyzed bioinformatically. It gave us prognostic data as a confirmation of whether it should be used as a biomarker. The expression level and pattern analysis were conducted using ONCOMINE, GENT2 and GEPIA2 online platforms. Samples with different clinical outcomes were investigated for expression and promoter methylation analysis was done in cancer vs normal tissues using UALCAN. The copy number alteration and mutation frequency and expression in different cancer studies were analyzed using cBioPortal. The PrognoScan and KM plotter survival analysis of significant data (p-value<0.05) was representing graphically. Pathway and Gene ontology analysis of gene correlated to TAP1 gene was presented using bar charts. After arranging the data in a single panel and correlating expression to prognosis, understanding mutational and alterations and comparing pathways, TAP1 may be a potential novel target to evade a threat against chemotherapy and the study gives new aspects to consider for immunotherapy in human breast, lung, liver and ovarian cancer.

scholarly journals FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

2018 ◽  
Vol 49 (5) ◽  
pp. 1766-1777 ◽  
Author(s):  
Jie Li ◽  
Songlin Zhang ◽  
Meili Pei ◽  
Lei Wu ◽  
Yanli Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Transwell Assay ◽  
Mesenchymal Transition ◽  
Novel Target ◽  
Snail1 Expression

Background/Aims: Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. Snail1 has a pivotal role in the regulation of EMT, involving the loss of E-cadherin and concomitant upregulation of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian cancer cells, but the precise mechanism of FSCN1 in EMT process has not been clearly elucidated. Methods: The levels of FSCN1 and snail1 were determined in epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR. The changes of EMT makers and effects on snail1 by FSCN1 were examined by overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western blotting. The invasiveness of the FSCN1-modified EOC cells was examined in transwell assay. Co-immunoprecipitation (IP) was performed to detect the interaction between snail1 and FSCN1 in EOC cells. Results: We found FSCN1 and snail1 significantly increased in EOC, and especially in EOC with metastasis. FSCN1 was positively correlated with snail1 expression at the cellular/histological levels. Moreover, we further showed that FSCN1 physiologically interacted with and increased the levels of snail1 to promote ovarian cancer cell EMT. Conclusion: FSCN1 promote EMT through snail1 in ovarian cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and metastasis of EOC cells.

scholarly journals Transmission of X-linked Ovarian Cancer: Characterization and Implications

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
John Lewis Etter ◽  
Kirsten Moysich ◽  
Shaun Kohli ◽  
Shashikant Lele ◽  
Kunle Odunsi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
X Chromosome ◽  
Risk Allele ◽  
Significant Proportion ◽  
Distinct Pattern ◽  
Future Studies ◽  
Independent Locus ◽  
Familial Ovarian Cancer ◽  
Novel Target ◽  
Allele Transmission

We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies.

scholarly journals SPHK1 Is a Novel Target of Metformin in Ovarian Cancer

2019 ◽  
Vol 17 (4) ◽  
pp. 870-881 ◽  
Author(s):  
Peter C. Hart ◽  
Tatsuyuki Chiyoda ◽  
Xiaojing Liu ◽  
Melanie Weigert ◽  
Marion Curtis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Novel Target

scholarly journals Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132337 ◽  
Author(s):  
Dong-Jun Qin ◽  
Cai-Xia Tang ◽  
Li Yang ◽  
Hu Lei ◽  
Wei Wei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Target Molecule ◽  
Novel Target

Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer

2002 ◽  
Vol 2 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Martin J Cannon ◽  
Timothy J O’Brien ◽  
L Joey Underwood ◽  
Mark D Crew ◽  
Kristina L Bondurant ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cell ◽  
Novel Target

scholarly journals Cancer Stem Cells and Epithelial Ovarian Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sheetal Dyall ◽  
Simon A. Gayther ◽  
Dimitra Dafou
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Epithelial Ovarian Cancer ◽  
Primary Tumour ◽  
Cellular Level ◽  
Small Population ◽  
Novel Target

The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs), or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

Understanding the roles of RecQ helicases in the maintenance of genome integrity and suppression of tumorigenesis

2004 ◽  
Vol 32 (6) ◽  
pp. 957-958 ◽  
Author(s):  
H.W. Mankouri ◽  
I.D. Hickson
Keyword(s):  
Genome Stability ◽  
Molecular Level ◽  
Genome Instability ◽  
Cancer Predisposition ◽  
Genome Integrity ◽  
Recq Helicase ◽  
Recq Helicases ◽  
Evolutionarily Conserved ◽  
Clinical Disorders

RecQ helicases are evolutionarily conserved enzymes required for the maintenance of genome stability. Mutations in three of the five known human RecQ helicase genes cause distinct clinical disorders that are characterized by genome instability and cancer predisposition. Recent studies have begun to reveal the cellular roles of RecQ helicases and how these enzymes may prevent tumorigenesis at the molecular level.

scholarly journals N-terminal sumoylation of centromeric histone H3 variant Cse4 regulates its proteolysis to prevent mislocalization to non-centromeric chromatin

2017 ◽  
Author(s):  
Kentaro Ohkuni ◽  
Reuben Levy-Myers ◽  
Jack Warren ◽  
Wei-Chun Au ◽  
Yoshimitsu Takahashi ◽  
...  
Keyword(s):  
Genome Stability ◽  
Histone H3 ◽  
Physiological Role ◽  
Centromeric Chromatin ◽  
E3 Ligases ◽  
Physiological Conditions ◽  
Evolutionarily Conserved ◽  
Histone H3 Variant

AbstractStringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we identify lysine 65 (K65) in Cse4 as a SUMO site and show that sumoylation of Cse4 K65 regulates its ubiquitin-mediated proteolysis by Slx5. Strains expressing cse4 K65R exhibit reduced levels of sumoylated and ubiquitinated Cse4 in vivo. Furthermore, co-immunoprecipitation experiments reveal reduced interaction of cse4 K65R with Slx5. Defects in sumoylation of cse4 K65R contribute to increased stability and mislocalization of cse4 K65R under normal physiological conditions. Based on the increased stability of cse4 K65R in psh1∆ strains but not in slx5∆ strains, we conclude that Slx5 targets sumoylated Cse4 K65 for ubiquitination-mediated proteolysis independent of Psh1. In summary, we have identified and characterized the physiological role of Cse4 sumoylation and determined that sumoylation of Cse4 K65 regulates ubiquitin-mediated proteolysis and prevents mislocalization of Cse4 which is required for genome stability.

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