GSE128070 Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer

Contributors : Ewelina Szyma ńska ; Paulina Nowak ; Krzysztof Kolmus ; Magdalena Cybulska ; Krzysztof Goryca ; Edyta Derezińska-Wołek ; Anna Szumera-Ciećkiewicz ; Marta Brewińska-Olchowik ; Aleksandra Grochowska ; Katarzyna Piwocka ; Monika Prochorec-Sobieszek ; Michał Mikula ; Marta MiączyńskaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSomatic copy number alterations play a critical role in oncogenesis. Loss of chromosomal regions containing tumor suppressors can lead to collateral deletion of passenger genes. This can be exploited therapeutically if synthetic lethal partners of such passenger genes are known and represent druggable targets. Here, we report that VPS4B gene, encoding an ATPase involved in ESCRT-dependent membrane remodeling, is such a passenger gene frequently deleted in many cancer types, notably in colorectal cancer (CRC). We confirmed downregulation of VPS4B mRNA and protein levels from CRC patient samples. We identified VPS4A paralog as a synthetic lethal interactor for VPS4B in vitro and in mouse xenografts. Depleting both proteins profoundly altered the cellular transcriptome and induced cell death accompanied by the release of immunomodulatory molecules that mediate inflammatory and anti-tumor responses. Our results identify a pair of novel druggable targets for personalized oncology and provide a rationale to develop VPS4 inhibitors for precision therapy of VPS4B-deficient cancers.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 22 October 2019Source: Seminars in Cancer BiologyAuthor(s): Tamara T. Lah, Metka Novak, Barbara BreznikAbstractBrain, the major organ of the central nervous system controls and processes most of body activities. Therefore, the most aggressive brain tumor – glioblastoma and metastases from other organs to the brain are lethal leaving the patients with very short time of survival. The brain tissue landscape is very different from any other tissues and the specific microenvironment, comprising stem cells niches and blood-brain barrier, significantly influences the low rate of glioblast...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
ConclusionAt the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Conclusion: Our findings indicate that the CYP24A1 rs4809960 polymorphism decreased the risk of CRC in the studied population. PMID: 31802707 [PubMed - as supplied by publisher]
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
In this study, RT-PCR and western blotting were used to analyze the mRNA and protein expression, respectively; cell viability was assayed with MTS analysis; cell migration was measured with Trans-well analysis.Key findingsIn the present study, the results indicated that the mRNA levels of LSD1 and TSPAN8 in CRC were significantly higher than that in corresponding adjacent non-tumor tissue. Down-regulation of LSD1 or TSPAN8 as well as LSD1 inhibitor Tranylcypromine hemisulfate inhibited the proliferation and migration of CRC cells, while over-expression of LSD1 exhibited opposite effects. LSD1 up-regulated TSPAN8 expression...
Source: Life Sciences - Category: Biology Source Type: research
In conclusion, Melatonin possesses an antioxidant effect that can protect the sciatic nerve from degeneration and potentiate VCR's anticancer effect at the same time.
Source: Life Sciences - Category: Biology Source Type: research
Colorectal cancer (CRC) is the third most commonly diagnosed cancer. This review gives an overview of the current knowledge of molecular mechanisms of colorectal carcinogenesis and the role of molecular testing in the management of CRC. The majority of CRCs arise from precursor lesions such as adenoma, transforming to adenocarcinoma. Three molecular carcinogenesis pathways have been identified; (1) chromosomal instability, (2) microsatellite instability (MSI), and (3) CpG island methylator phenotype, each account for ~85%, 15%, and 17%, respectively. Evaluation of MSI status, extended RAS mutation analysis, and BRAF mutati...
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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