Pub Date : 2022-01-11eCollection Date: 2021-01-01DOI: 10.4161/23723556.2014.995020
Evangelos Pazarentzos
IκΒα (the protein product of NFKBIA gene) has widely been considered a pro- apoptotic factor due to its ability to inhibit the anti-apoptotic transcription factor NFκB. Our findings indicate that IκΒα also exerts a strong anti-apoptotic activity at the outer mitochondria membrane (OMM). This function we uncovered is distinct from its ability to sequester and inhibit NFκB. IκΒα instead binds to voltage dependent anion channel 1 (VDAC1) and Hexokinase 2 (HK2), stabilizes this complex and prevents mitochondria outer membrane permeabilisation (MOMP) and apoptosis.
{"title":"Cell demise inhibited: Unexpected liaisons between mitochondria and IκΒα.","authors":"Evangelos Pazarentzos","doi":"10.4161/23723556.2014.995020","DOIUrl":"10.4161/23723556.2014.995020","url":null,"abstract":"<p><p>IκΒα (the protein product of <i>NFKBIA</i> gene) has widely been considered a pro- apoptotic factor due to its ability to inhibit the anti-apoptotic transcription factor NFκB. Our findings indicate that IκΒα also exerts a strong anti-apoptotic activity at the outer mitochondria membrane (OMM). This function we uncovered is distinct from its ability to sequester and inhibit NFκB. IκΒα instead binds to voltage dependent anion channel 1 (VDAC1) and Hexokinase 2 (HK2), stabilizes this complex and prevents mitochondria outer membrane permeabilisation (MOMP) and apoptosis.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70555083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-03eCollection Date: 2023-01-01DOI: 10.1080/23723556.2021.2014734
Subramanian Venkatesan, Mihaela Angelova, Jirina Bartkova, Samuel F Bakhoum, Jiri Bartek, Nnennaya Kanu, Charles Swanton
Our recent study revealed that APOBEC3B is upregulated during the preinvasive stages of non-small cell lung cancer and breast cancer. In addition to its role in mediating single nucleotide variants, we propose that APOBEC3 promotes copy number intratumor heterogeneity prior to invasion, providing a substrate for cancer evolution.
{"title":"APOBEC3 as a driver of genetic intratumor heterogeneity.","authors":"Subramanian Venkatesan, Mihaela Angelova, Jirina Bartkova, Samuel F Bakhoum, Jiri Bartek, Nnennaya Kanu, Charles Swanton","doi":"10.1080/23723556.2021.2014734","DOIUrl":"10.1080/23723556.2021.2014734","url":null,"abstract":"<p><p>Our recent study revealed that APOBEC3B is upregulated during the preinvasive stages of non-small cell lung cancer and breast cancer. In addition to its role in mediating single nucleotide variants, we propose that APOBEC3 promotes copy number intratumor heterogeneity prior to invasion, providing a substrate for cancer evolution.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47306257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1080/23723556.2022.2078628
Ma de Lourdes Zuñiga Martinez, Carlos Miguel López Mendoza, Jared Tenorio Salazar, Alejandro Manuel García Carrancá, Marco Antonio Cerbón Cervantes, Luz Eugenia Alcántara-Quintana
Cell lines have been considered excellent research models in many areas of biomedicine and, specifically, in the study of carcinogenesis. However, they cease to be effective models if their behavior changes. Although studies on the cross-contamination of cell lines originating from different tissues have been performed, little is known about cell lines derived from cervical neoplasia. We know that high-risk HPV (HR-HPV) is associated with the development of this type of cancer. This link between HPV infection and cancer was first established over 35 years ago when HPV16 DNA was found to be present in a large proportion of cervical cancer biopsies. The present review paper aims to report the status of the establishment, authenticity, and characterization of cervical cancer (CC) cell lines. This is a systematic review of articles on the establishment, authenticity, and characterization of CC cell lines, published from 1960 to date in the databases and in cell repository databases. 52 cell lines were identified in the literature. Only 25 cell lines were derived from cervical neoplasia, of which only 45.8% have a reported identity test (genomic fingerprint). Despite the increase in the establishment of cell lines of cervical neoplasia and the standards for the regulation of these study models, the criteria for their characterization continue to be diverse.
{"title":"Establishment, authenticity, and characterization of cervical cancer cell lines.","authors":"Ma de Lourdes Zuñiga Martinez, Carlos Miguel López Mendoza, Jared Tenorio Salazar, Alejandro Manuel García Carrancá, Marco Antonio Cerbón Cervantes, Luz Eugenia Alcántara-Quintana","doi":"10.1080/23723556.2022.2078628","DOIUrl":"https://doi.org/10.1080/23723556.2022.2078628","url":null,"abstract":"<p><p>Cell lines have been considered excellent research models in many areas of biomedicine and, specifically, in the study of carcinogenesis. However, they cease to be effective models if their behavior changes. Although studies on the cross-contamination of cell lines originating from different tissues have been performed, little is known about cell lines derived from cervical neoplasia. We know that high-risk HPV (HR-HPV) is associated with the development of this type of cancer. This link between HPV infection and cancer was first established over 35 years ago when HPV16 DNA was found to be present in a large proportion of cervical cancer biopsies. The present review paper aims to report the status of the establishment, authenticity, and characterization of cervical cancer (CC) cell lines. This is a systematic review of articles on the establishment, authenticity, and characterization of CC cell lines, published from 1960 to date in the databases and in cell repository databases. 52 cell lines were identified in the literature. Only 25 cell lines were derived from cervical neoplasia, of which only 45.8% have a reported identity test (genomic fingerprint). Despite the increase in the establishment of cell lines of cervical neoplasia and the standards for the regulation of these study models, the criteria for their characterization continue to be diverse.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10432933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-14eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.2007028
Xavier Renaudin, Ashok R Venkitaraman
How oxidative stress promotes aging-related human diseases like cancer and neurodegeneration remains unclear. Here, we discuss the origins and implications of an oxidative-stress response recently reported to destabilize the mitochondrial (mt) genome via unscheduled RNA/DNA hybrid (R-loop) accumulation, by impairing the recruitment of RNAseH1 to the regulatory regions of mtDNA.
{"title":"A mitochondrial response to oxidative stress mediated by unscheduled RNA-DNA hybrids (R-loops).","authors":"Xavier Renaudin, Ashok R Venkitaraman","doi":"10.1080/23723556.2021.2007028","DOIUrl":"10.1080/23723556.2021.2007028","url":null,"abstract":"<p><p>How oxidative stress promotes aging-related human diseases like cancer and neurodegeneration remains unclear. Here, we discuss the origins and implications of an oxidative-stress response recently reported to destabilize the mitochondrial (mt) genome via unscheduled RNA/DNA hybrid (R-loop) accumulation, by impairing the recruitment of RNAseH1 to the regulatory regions of mtDNA.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41787791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-19eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.2003161
Fabrizio Simeoni, Tim Cp Somervaille
Tissue-inappropriate expression of FOXC1 (Forkhead Box C1) in acute myeloid leukemia confers a monocyte/macrophage lineage differentiation block. We discovered that FOXC1 interacts with RUNX1 (Runt-Related Transcription Factor 1) to stabilize a RUNX1, HDAC1 (Histone Deacetylase 1) and TLE3 (Transducin-like enhancer protein 3) repressor complex at enhancers controlling myeloid differentiation genes.
{"title":"Enhancer recruitment of a RUNX1, HDAC1 and TLE3 co-repressor complex by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia.","authors":"Fabrizio Simeoni, Tim Cp Somervaille","doi":"10.1080/23723556.2021.2003161","DOIUrl":"10.1080/23723556.2021.2003161","url":null,"abstract":"<p><p>Tissue-inappropriate expression of <i>FOXC1</i> (Forkhead Box C1) in acute myeloid leukemia confers a monocyte/macrophage lineage differentiation block. We discovered that FOXC1 interacts with RUNX1 (Runt-Related Transcription Factor 1) to stabilize a RUNX1, HDAC1 (Histone Deacetylase 1) and TLE3 (Transducin-like enhancer protein 3) repressor complex at enhancers controlling myeloid differentiation genes.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41889564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-16DOI: 10.1080/23723556.2021.2000318
Amanda K Riley, Alice H Berger
In recent work, we performed CRISPR/Cas9 screening in RIT1 (Ras-like in all tissues)-mutant cancer cells. We found that RIT1-mutant cells are vulnerable to loss of mitotic regulators, and mutant RIT1 synergizes with YAP1 (yes-associated protein 1) in oncogenesis. These findings can be leveraged to identify targeted therapies for RIT1-mutant cancer.
{"title":"Genome-wide CRISPR screening reveals novel therapeutic targets in RIT1-driven lung cancer.","authors":"Amanda K Riley, Alice H Berger","doi":"10.1080/23723556.2021.2000318","DOIUrl":"https://doi.org/10.1080/23723556.2021.2000318","url":null,"abstract":"<p><p>In recent work, we performed CRISPR/Cas9 screening in <i>RIT1 (Ras-like in all tissues)-</i>mutant cancer cells. We found that <i>RIT1</i>-mutant cells are vulnerable to loss of mitotic regulators, and mutant RIT1 synergizes with YAP1 (yes-associated protein 1) in oncogenesis. These findings can be leveraged to identify targeted therapies for <i>RIT1</i>-mutant cancer.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997261/pdf/KMCO_8_2000318.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-09eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1997040
Bi Shi, Wei Li, Hao Jiang
Alterations of epigenetic modulators are extensively associated with cancer, but their key molecular activities in cancer regulation are often unclear. We discovered that lysine demethylase 6A (KDM6A, also known as UTX) suppresses cancer by forming liquid-like condensates with lysine methyltransferase 2D (KMT2D, also known as MLL4) and regulating chromatin activity at multiple levels.
{"title":"Epigenetic condensates regulate chromatin activity and tumorigenesis.","authors":"Bi Shi, Wei Li, Hao Jiang","doi":"10.1080/23723556.2021.1997040","DOIUrl":"https://doi.org/10.1080/23723556.2021.1997040","url":null,"abstract":"<p><p>Alterations of epigenetic modulators are extensively associated with cancer, but their key molecular activities in cancer regulation are often unclear. We discovered that lysine demethylase 6A (KDM6A, also known as UTX) suppresses cancer by forming liquid-like condensates with lysine methyltransferase 2D (KMT2D, also known as MLL4) and regulating chromatin activity at multiple levels.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/d8/KMCO_8_1997040.PMC8632315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39688332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-02DOI: 10.1080/23723556.2021.1989262
Yuan Zhu, Wang Zheng, Emmanuelle S. Jecrois, Brianna R. Pierce, Daniel M. Treisman
ABSTRACT Pediatric low-grade gliomas (pLGGs) are almost universally driven by abnormal activation of RAS-mediated MEK-ERK/MAPK signaling pathway. pLGGs predominantly occur in children, suggesting that they originate in an ERK-dependent neural stem/progenitor population(s) transiently present in the developing brain. Our recent preclinical study reveals a cell-lineage-of-origin and develops a chemopreventative therapeutic strategy.
{"title":"A therapeutic window for preventive therapy in NF1-associated optic pathway glioma","authors":"Yuan Zhu, Wang Zheng, Emmanuelle S. Jecrois, Brianna R. Pierce, Daniel M. Treisman","doi":"10.1080/23723556.2021.1989262","DOIUrl":"https://doi.org/10.1080/23723556.2021.1989262","url":null,"abstract":"ABSTRACT Pediatric low-grade gliomas (pLGGs) are almost universally driven by abnormal activation of RAS-mediated MEK-ERK/MAPK signaling pathway. pLGGs predominantly occur in children, suggesting that they originate in an ERK-dependent neural stem/progenitor population(s) transiently present in the developing brain. Our recent preclinical study reveals a cell-lineage-of-origin and develops a chemopreventative therapeutic strategy.","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44070503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-02DOI: 10.1080/23723556.2021.1997331
S. Fröhling
ABSTRACT For most rare cancers, precision oncology approaches are not established because these entities are poorly understood and their investigation requires the collaboration of many centers. The MASTER precision oncology network demonstrates that clinical whole-genome/exome and RNA sequencing yield molecular mechanism-aware treatments that benefit a substantial proportion of patients with advanced rare cancers and will prepare the ground for future clinical trials.
{"title":"Interdisciplinary team science to understand and intercept rare cancers","authors":"S. Fröhling","doi":"10.1080/23723556.2021.1997331","DOIUrl":"https://doi.org/10.1080/23723556.2021.1997331","url":null,"abstract":"ABSTRACT For most rare cancers, precision oncology approaches are not established because these entities are poorly understood and their investigation requires the collaboration of many centers. The MASTER precision oncology network demonstrates that clinical whole-genome/exome and RNA sequencing yield molecular mechanism-aware treatments that benefit a substantial proportion of patients with advanced rare cancers and will prepare the ground for future clinical trials.","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47283118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-02DOI: 10.1080/23723556.2021.2002120
C. G. Langdon, M. Hatley
ABSTRACT Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis.
{"title":"The perfect PTEN – transcriptional regulation by PTEN dictates sarcoma identity","authors":"C. G. Langdon, M. Hatley","doi":"10.1080/23723556.2021.2002120","DOIUrl":"https://doi.org/10.1080/23723556.2021.2002120","url":null,"abstract":"ABSTRACT Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis.","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43439788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}