<i>TP53</i> Mutation by CRISPR System Enhances the Malignant Potential of Colon Cancer

Watanabe, Sho; Tsuchiya, Kiichiro; Nishimura, Ryu; Shirasaki, Tetsuya; Katsukura, Nobuhiro; Hibiya, Shuji; Okamoto, Ryuichi; Nakamura, Toshio; Watanabe, Mamoru

doi:10.1158/1541-7786.mcr-18-1195

Cited by 18 publications

(11 citation statements)

References 36 publications

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“…UBR5 has been reported to be a regulator of the p53 protein, a tumor suppressor 25,26 . Compromised p53 expression and loss of function mutations in TP53 contribute to the generation of cancer stem cells (CSCs) [27][28][29] . Consistently, we observed an elevated p53 protein level in ID8/ Ubr5 -/tumor compared to WT tumor, whereas in UBR5overexpressing ID8/GFP tumor, p53 level was decreased (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages

et al. 2020

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Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.

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Section: Resultsmentioning

confidence: 99%

Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages

et al. 2020

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“…The high-risk group showed high TP53 mutation frequency whether in TCGA-LUAD or GSE72094. TP53 mutation is an adverse prognostic factor for advanced non-small-cell lung cancer (NSCLC) ( Jiao et al, 2018 ) and a hallmark event of advanced sporadic colon cancer ( Watanabe et al, 2019 ). Moreover, Haupt et al (2019) found that high TP53 frequency and P53 network dysregulation trigger low survival rate of male cancer patients in North America.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Prognostic Markers of Lung Adenocarcinoma Based on Tumor Metabolism-Related Genes

Zhang

Cheng³

2021

Front. Genet.

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Lung adenocarcinoma (LUAD) is a prevalent cancer killer. Investigation on potential prognostic markers of LUAD is crucial for a patient’s postoperative planning. LUAD-associated datasets were acquired from Gene Expression Omnibus (GEO) as well as The Cancer Genome Atlas (TCGA). LUAD metabolism-associated differentially expressed genes were obtained, combining tumor metabolism-associated genes. COX regression analyses were conducted to build a five-gene prognostic model. Samples were divided into high- and low-risk groups by the established model. Survival analysis displayed favorable prognosis in the low-risk group in the training set. Favorable predictive performance of the model was discovered as hinted by receiver’s operative curve (ROC). Survival analysis and ROC analysis in the validation set held an agreement. Gene Set Enrichment Analysis (GSEA), tumor mutation bearing (TMB), and immune infiltration differential analysis were performed. The two groups displayed differences in glycolysis gluconeogenesis, P53 signaling pathway, etc. The high-risk group showed higher TP53 mutation frequency as well as TMB. The low-risk group displayed higher immune activity along with immune score. Altogether, this study casts light on further development of novel prognostic markers for LUAD.

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“…2019) e a proteína TP53 no câncer de cólon (WATANABE et al, 2019) tiveram mutações induzidas por CRISPR/Cas9 a fim de avaliar a progressão tumoral, que foi acentuada e, no caso de TP53, ainda houve aumento da quimiorresistência (WATANABE et al, 2019).…”

Section: Discussionunclassified

CRISPR: Edição genômica aplicada à Oncologia / CRISPR: Genomic editing applied to Oncology

Bresolin¹,

Wiethölter²,

Kirsten³

2021

BJDV

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O sistema CRISPR é uma ferramenta de engenharia genômica, que foi descoberta, inicialmente, como um mecanismo de imunidade bacteriana contra vírus invasores, sendo adaptada, posteriormente, para edição gênica em células de mamíferos. A técnica sobrepôs-se às surgidas anteriormente por ser extremamente versátil, simples, específica e de baixo custo. O câncer é caracterizado por ser uma doença que apresenta acúmulo de múltiplas alterações genéticas e epigenéticas no genoma, podendo, assim, ser alvo da técnica CRISPR a fim de modificar genes envolvidos com a doença, buscar novas alternativas de tratamento e criar modelos de estudo. Com base nisso, o objetivo deste estudo é descrever como o sistema CRISPR tem sido aplicado na Oncologia. O trabalho trata-se de uma revisão de literatura, buscando reunir e sintetizar resultados acerca da aplicação de CRISPR no câncer e os principais tipos de neoplasias que são alvos da técnica. A coleta de informações foi realizada nas bases de dados Bireme e Pubmed por meio dos descritores "sistema CRISPR-Cas" e "neoplasias", nos idiomas português e inglês. Os critérios de inclusão envolveram a utilização de artigos na íntegra, no idioma inglês e publicados nos últimos 6 anos, totalizando 20 artigos. Tendo em vista que o câncer está entre as principais causas de morte e de problemas de saúde pública, e sabendo que se trata de uma doença causada por alterações genéticas, CRISPR surge como uma técnica promissora na pesquisa, diagnóstico e tratamento dessa patologia. A técnica tem sido utilizada, principalmente, para o silenciamento de oncogenes e genes supressores de tumor, tanto in vitro quanto in vivo, a fim de obter modelos de estudo e avaliar o envolvimento de genes no processo de tumorigênese. Esses resultados satisfatórios sugerem que a aplicação da técnica na Oncologia é promissora e sua utilização

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TP53 Mutation by CRISPR System Enhances the Malignant Potential of Colon Cancer

Cited by 18 publications

References 36 publications

Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages

Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages

Investigation of Prognostic Markers of Lung Adenocarcinoma Based on Tumor Metabolism-Related Genes

CRISPR: Edição genômica aplicada à Oncologia / CRISPR: Genomic editing applied to Oncology

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