Molecular Oncology最新文献_第4页

Targeted inhibition of STAT3 induces immunogenic cell death of hepatocellular carcinoma cells via glycolysis 靶向抑制STAT3可通过糖酵解诱导肝癌细胞免疫原性死亡

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-05 DOI: 10.1002/1878-0261.13263

Ya Li, Zhenwei Song, Qiuju Han, Huajun Zhao, Zhaoyi Pan, Z. Lei, Jian Zhang

{"title":"Targeted inhibition of STAT3 induces immunogenic cell death of hepatocellular carcinoma cells via glycolysis","authors":"Ya Li, Zhenwei Song, Qiuju Han, Huajun Zhao, Zhaoyi Pan, Z. Lei, Jian Zhang","doi":"10.1002/1878-0261.13263","DOIUrl":"https://doi.org/10.1002/1878-0261.13263","url":null,"abstract":"In hepatocellular carcinoma (HCC), the signal transducer and activator of transcription 3 (STAT3) is present in an overactive state that is closely related to tumour development and immune escape. STAT3 inhibition reshapes the tumour immune microenvironment, but the underlying mechanisms have not been fully clarified. We found that STAT3 inhibition could induce immunogenic cell death (ICD) of HCC cells via translocation of the “eat me” molecule calreticulin to the cell surface and a significant reduction in the expression of the “don’t eat me” molecule leucocyte surface antigen CD47. STAT3 inhibition promoted dendritic cell (DC) activation and enhanced the recognition and phagocytosis of HCC cells by macrophages. Furthermore, STAT3 inhibition prevented the expression of key glycolytic enzymes, facilitating the induction of ICD in HCC. Interestingly, STAT3 directly regulated the transcription of CD47 and solute carrier family 2 member 1 (SLC2A1; also known as GLUT1). In subcutaneous and orthotopic transplantation mouse tumour models, the STAT3 inhibitor napabucasin prevented tumour growth and induced the expression of calreticulin and the protein disulfide isomerase family A member 3 (PDIA3; also known as ERp57) but suppressed that of CD47 and GLUT1. Meanwhile, the amount of tumour‐infiltrated DCs and macrophages increased, along with the expression of costimulatory molecules. More CD4+ and CD8+ T cells accumulated in tumour tissues, and CD8+ T cells had lower expression of checkpoint molecules such as lymphocyte activation gene 3 protein (LAG‐3) and programmed cell death protein 1 (PD‐1). Significantly, the antitumour immune memory response was induced by treatment targeting STAT3. These findings provide a new mechanism for targeting STAT3‐induced ICD in HCC, and confirms STAT3 as a potential target for the treatment of HCC via reshaping the tumour immune microenvironment.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2861 - 2880"},"PeriodicalIF":6.6,"publicationDate":"2022-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43065349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Issue Information 问题信息

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-01 DOI: 10.1002/1878-0261.12994

引用次数: 0

MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers MGMT失活作为晚期胆道癌患者的一种新生物标志物

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-27 DOI: 10.1002/1878-0261.13256

M. Niger, F. Nichetti, A. Casadei‐Gardini, F. Morano, C. Pircher, E. Tamborini, F. Perrone, M. Canale, D. Lipka, A. Vingiani, L. Agnelli, A. Dobberkau, J. Hüllein, Felix Korell, C. Heilig, S. Pusceddu, F. Corti, M. Droz, P. Ulivi, M. Prisciandaro, M. Antista, M. Bini, L. Cattaneo, M. Milione, H. Glimm, B. Köhler, G. Pruneri, D. Hübschmann, S. Fröhling, V. Mazzaferro, F. Pietrantonio, M. Di Bartolomeo, F. de Braud

{"title":"MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers","authors":"M. Niger, F. Nichetti, A. Casadei‐Gardini, F. Morano, C. Pircher, E. Tamborini, F. Perrone, M. Canale, D. Lipka, A. Vingiani, L. Agnelli, A. Dobberkau, J. Hüllein, Felix Korell, C. Heilig, S. Pusceddu, F. Corti, M. Droz, P. Ulivi, M. Prisciandaro, M. Antista, M. Bini, L. Cattaneo, M. Milione, H. Glimm, B. Köhler, G. Pruneri, D. Hübschmann, S. Fröhling, V. Mazzaferro, F. Pietrantonio, M. Di Bartolomeo, F. de Braud","doi":"10.1002/1878-0261.13256","DOIUrl":"https://doi.org/10.1002/1878-0261.13256","url":null,"abstract":"Biliary tract cancers (BTCs) have poor prognosis and limited therapeutic options. The impact of O6‐methylguanine‐DNA methyltransferase (MGMT) inactivation in advanced BTC patients is not established. We investigated the prevalence, prognostic, and predictive impact of MGMT inactivation in two multicenter cohorts. MGMT inactivation was assessed through PCR and immunohistochemistry (IHC) in an Italian cohort; the results were then externally validated using RNA sequencing (RNA‐seq) data from the BTC subcohort of the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) precision oncology program of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Among 164 Italian cases, 18% presented MGMT promoter hypermethylation (> 14%) and 73% had negative MGMT protein expression. Both were associated with worse overall survival (OS; HR 2.31; P < 0.001 and HR 1.99, P = 0.012, respectively). In the MASTER cohort, patients with lower MGMT mRNA expression showed significantly poorer OS (median OS [mOS] 20.4 vs 31.7 months, unadjusted HR 1.89; P = 0.043). Our results suggest that MGMT inactivation is a frequent epigenetic alteration in BTC, with a significant prognostic impact, and provide the rationale to explore DNA‐damaging agents in MGMT‐inactivated BTCs.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2733 - 2746"},"PeriodicalIF":6.6,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44275522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Anticancer function of microRNA‐30e is mediated by negative regulation of HELLPAR , a noncoding macroRNA, and genes involved in ubiquitination and cell cycle progression in prostate cancer 微小RNA-30e的抗癌功能是由HELLPAR（一种非编码的大分子RNA）和参与前列腺癌症泛素化和细胞周期进展的基因的负调控介导的

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-25 DOI: 10.1002/1878-0261.13255

Kavya Ganapathy, Christopher Ngo, T. Andl, D. Coppola, Jong Park, R. Chakrabarti

{"title":"Anticancer function of microRNA‐30e is mediated by negative regulation of HELLPAR , a noncoding macroRNA, and genes involved in ubiquitination and cell cycle progression in prostate cancer","authors":"Kavya Ganapathy, Christopher Ngo, T. Andl, D. Coppola, Jong Park, R. Chakrabarti","doi":"10.1002/1878-0261.13255","DOIUrl":"https://doi.org/10.1002/1878-0261.13255","url":null,"abstract":"Prostate cancer (PCa) progression relies on androgen receptor (AR) function, making AR a top candidate for PCa therapy. However, development of drug resistance is common, which eventually leads to development of castration‐resistant PCa. This warrants a better understanding of the pathophysiology of PCa that facilitates the aberrant activation of key signaling pathways including AR. MicroRNAs (miRNAs) function as regulators of cancer progression as they modulate various cellular processes. Here, we demonstrate a multidimensional function of miR‐30e through the regulation of genes involved in various signaling pathways. We noted loss of miR‐30e expression in prostate tumors, which, when restored, led to cell cycle arrest, induction of apoptosis, improved drug sensitivity of PCa cells and reduced tumor progression in xenograft models. We show that experimental upregulation of miR‐30e reduces expression of mRNAs including AR, FBXO45, SRSF7 and MYBL2 and a novel long noncoding RNA (lncRNA) HELLPAR, which are involved in cell cycle, apoptosis and ubiquitination, and the effects could be rescued by inhibition of miR‐30e expression. RNA immunoprecipitation analysis confirmed direct interactions between miR‐30e and its RNA targets. We noted a newly identified reciprocal relationship between miR‐30e and HELLPAR, as inhibition of HELLPAR improved stabilization of miR‐30e. Transcriptome profiling and quantitative real‐time PCR (qRT‐PCR) validation of miR‐30e‐expressing PCa cells showed differential expression of genes involved in cell cycle progression, apoptosis and ubiquitination, which supports our in vitro study. This study demonstrates an integrated function of miR‐30e on dysregulation of miRNA/lncRNA/mRNA axes that may have diagnostic and therapeutic significance in aggressive PCa.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2936 - 2958"},"PeriodicalIF":6.6,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47799125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Altered splicing of ATG16‐L1 mediates acquired resistance to tyrosine kinase inhibitors of EGFR by blocking autophagy in non‐small cell lung cancer ATG16‐L1剪接改变通过阻断非小细胞肺癌的自噬介导对EGFR酪氨酸激酶抑制剂的获得性耐药

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-20 DOI: 10.1002/1878-0261.13229

Anne-Sophie Hatat, C. Benoit-Pilven, Amélie Pucciarelli, F. de Fraipont, Lucie Lamothe, P. Perron, Amandine Rey, M. Giaj Levra, A. Toffart, D. Auboeuf, B. Eymin, S. Gazzeri

{"title":"Altered splicing of ATG16‐L1 mediates acquired resistance to tyrosine kinase inhibitors of EGFR by blocking autophagy in non‐small cell lung cancer","authors":"Anne-Sophie Hatat, C. Benoit-Pilven, Amélie Pucciarelli, F. de Fraipont, Lucie Lamothe, P. Perron, Amandine Rey, M. Giaj Levra, A. Toffart, D. Auboeuf, B. Eymin, S. Gazzeri","doi":"10.1002/1878-0261.13229","DOIUrl":"https://doi.org/10.1002/1878-0261.13229","url":null,"abstract":"Despite the initial efficacy of using tyrosine kinase inhibitors of epidermal growth factor receptors (EGFR‐TKIs) for treating patients with non‐small cell lung cancer (NSCLC), resistance inevitably develops. Recent studies highlight a link between alternative splicing and cancer drug response. Therefore, we aimed to identify deregulated splicing events that play a role in resistance to EGFR‐TKI. By using RNA sequencing, reverse‐transcription PCR (RT‐PCR), and RNA interference, we showed that overexpression of a splice variant of the autophagic gene ATG16‐L1 that retains exon 8 and encodes the β‐isoform of autophagy‐related protein 16‐1 (ATG16‐L1 β) concurs acquired resistance to EGFR‐TKI in NSCLC cells. Using matched biopsies, we found increased levels of ATG16‐L1 β at the time of progression in 3 of 11 NSCLC patients treated with EGFR‐TKI. Mechanistically, gefitinib‐induced autophagy was impaired in resistant cells that accumulated ATG16‐L1 β. Neutralization of ATG16‐L1 β restored autophagy in response to gefitinib, induced apoptosis, and inhibited the growth of in ovo tumor xenografts. Conversely, overexpression of ATG16‐L1 β in parental sensitive cells prevented gefitinib‐induced autophagy and increased cell survival. These results support a role of defective autophagy in acquired resistance to EGFR‐TKIs and identify splicing regulation of ATG16‐L1 as a therapeutic vulnerability that could be explored for improving EGFR‐targeted cancer therapy.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3490 - 3508"},"PeriodicalIF":6.6,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41356081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer ∆Np73效应子的深入蛋白质组学表征确定了与结直肠癌淋巴管生成、血管生成和转移相关的具有诊断潜力的关键蛋白质

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-19 DOI: 10.1002/1878-0261.13228

María Garranzo-Asensio, J. Rodriguez-Cobos, C. S. Millán, C. Poves, M. Fernández-Aceñero, Daniel Pastor-Morate, D. Viñal, A. Montero‐Calle, G. Solís‐Fernández, M. Cerón, Manuel Gámez-Chiachio, N. Rodríguez, A. Guzman-Aranguez, R. Barderas, Gemma Domínguez

{"title":"In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer","authors":"María Garranzo-Asensio, J. Rodriguez-Cobos, C. S. Millán, C. Poves, M. Fernández-Aceñero, Daniel Pastor-Morate, D. Viñal, A. Montero‐Calle, G. Solís‐Fernández, M. Cerón, Manuel Gámez-Chiachio, N. Rodríguez, A. Guzman-Aranguez, R. Barderas, Gemma Domínguez","doi":"10.1002/1878-0261.13228","DOIUrl":"https://doi.org/10.1002/1878-0261.13228","url":null,"abstract":"Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer‐related death worldwide. Alterations in proteins of the p53‐family are a common event in CRC. ΔNp73, a p53‐family member, shows oncogenic properties and its effectors are largely unknown. We performed an in‐depth proteomics characterization of transcriptional control by ∆Np73 of the secretome of human colon cancer cells and validated its clinical potential. The secretome was analyzed using high‐density antibody microarrays and stable isotopic metabolic labeling. Validation was performed by semiquantitative PCR, ELISA, dot‐blot and western blot analysis. Evaluation of selected effectors was carried out using 60 plasma samples from CRC patients, individuals carrying premalignant colorectal lesions and colonoscopy‐negative controls. In total, 51 dysregulated proteins were observed showing at least 1.5‐foldchange in expression. We found an important association between the overexpression of ∆Np73 and effectors related to lymphangiogenesis, vasculogenesis and metastasis, such as brain‐derived neurotrophic factor (BDNF) and the putative aminoacyl tRNA synthase complex‐interacting multifunctional protein 1 (EMAP‐II)–vascular endothelial growth factor C–vascular endothelial growth factor receptor 3 axis. We further demonstrated the usefulness of BDNF as a potential CRC biomarker able to discriminate between CRC patients and premalignant individuals from controls with high sensitivity and specificity.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2672 - 2692"},"PeriodicalIF":6.6,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43942494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Fractionated irradiation of MCF7 breast cancer cells rewires a gene regulatory circuit towards a treatment‐resistant stemness phenotype MCF7乳腺癌症细胞的部分照射重新连接基因调节回路，使其具有治疗抗性的干性表型

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-17 DOI: 10.1002/1878-0261.13226

Auchi Inalegwu, Bart Cuypers, J. Claesen, A. Janssen, Amelie Coolkens, S. Baatout, K. Laukens, W. D. De Vos, R. Quintens

{"title":"Fractionated irradiation of MCF7 breast cancer cells rewires a gene regulatory circuit towards a treatment‐resistant stemness phenotype","authors":"Auchi Inalegwu, Bart Cuypers, J. Claesen, A. Janssen, Amelie Coolkens, S. Baatout, K. Laukens, W. D. De Vos, R. Quintens","doi":"10.1002/1878-0261.13226","DOIUrl":"https://doi.org/10.1002/1878-0261.13226","url":null,"abstract":"Radiotherapy is the standard of care for breast cancer. However, surviving radioresistant cells can repopulate following treatment and provoke relapse. Better understanding of the molecular mechanisms of radiation resistance may help to improve treatment of radioresistant tumours. To emulate radiation therapy at the cellular level, we exposed MCF7 breast cancer cells to daily radiation doses of 2 Gy up to an accumulated dose of 20 Gy. Fractionally irradiated cells (FIR20) displayed increased clonogenic survival and population doubling time as compared with age‐matched sham‐irradiated cells and untreated parental MCF7 cells. RNA‐sequencing revealed a core signature of 229 mRNAs and 7 circular RNAs of which the expression was significantly altered in FIR20 cells. Dysregulation of several top genes was mirrored at the protein level. The FIR20 cell transcriptome overlapped significantly with canonical radiation response signatures and demonstrated a remarkable commonality with radiation and endocrine therapy resistance expression profiles, suggesting crosstalk between both acquired resistance pathways, as indicated by reduced sensitivity to tamoxifen cytotoxicity of FIR20 cells. Using predictive analyses and functional enrichment, we identified a gene‐regulatory network that promotes stemness and inflammatory signalling in FIR20 cells. We propose that these phenotypic traits render breast cancer cells more radioresistant but may at the same time serve as potential targets for combination therapies.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3410 - 3435"},"PeriodicalIF":6.6,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42697242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

In situ expression of ERG protein in the context of tumor heterogeneity identifies prostate cancer patients with inferior prognosis 肿瘤异质性背景下ERG蛋白的原位表达可识别预后较差的前列腺癌患者

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-16 DOI: 10.1002/1878-0261.13225

Susanne G. Kidd, Mari Bogaard, K. Carm, A. C. Bakken, Aase V Maltau, M. Løvf, R. Lothe, K. Axcrona, U. Axcrona, R. Skotheim

{"title":"In situ expression of ERG protein in the context of tumor heterogeneity identifies prostate cancer patients with inferior prognosis","authors":"Susanne G. Kidd, Mari Bogaard, K. Carm, A. C. Bakken, Aase V Maltau, M. Løvf, R. Lothe, K. Axcrona, U. Axcrona, R. Skotheim","doi":"10.1002/1878-0261.13225","DOIUrl":"https://doi.org/10.1002/1878-0261.13225","url":null,"abstract":"Prognostic biomarkers for prostate cancer are needed to improve prediction of disease course and guide treatment decisions. However, biomarker development is complicated by the common multifocality and heterogeneity of the disease. We aimed to determine the prognostic value of candidate biomarkers transcriptional regulator ERG and related ETS family genes, while considering tumor heterogeneity. In a multisampled, prospective, and treatment‐naïve radical prostatectomy cohort from one tertiary center (2010–2012, median follow‐up 8.1 years), we analyzed ERG protein (480 patients; 2047 tissue cores), and RNA of several ETS genes in a subcohort (165 patients; 778 fresh‐frozen tissue samples). Intra‐ and interfocal heterogeneity was identified in 29% and 33% (ERG protein) and 39% and 27% (ETS RNA) of patients, respectively. ERG protein and ETS RNA was identified exclusively in a nonindex tumor in 31% and 32% of patients, respectively. ERG protein demonstrated independent prognostic value in predicting biochemical (P = 0.04) and clinical recurrence (P = 0.004) and appeared to have greatest prognostic value for patients with Grade Groups 4–5. In conclusion, when heterogeneity is considered, ERG protein is a robust prognostic biomarker for prostate cancer.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2810 - 2822"},"PeriodicalIF":6.6,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46129252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers 结直肠癌细胞和患者外泌体的脂质组学分析揭示了潜在的生物标志物

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-06 DOI: 10.1002/1878-0261.13223

M. Elmallah, P. Ortega-Deballon, Laure Hermite, Jean-Paul Pais-de-Barros, J. Gobbo, C. Garrido

{"title":"Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers","authors":"M. Elmallah, P. Ortega-Deballon, Laure Hermite, Jean-Paul Pais-de-Barros, J. Gobbo, C. Garrido","doi":"10.1002/1878-0261.13223","DOIUrl":"https://doi.org/10.1002/1878-0261.13223","url":null,"abstract":"Strong evidence suggests that differences in the molecular composition of lipids in exosomes depend on the cell type and has an influence on cancer initiation and progression. Here, we analyzed by liquid chromatography–mass spectrometry (LC‐MS) the lipidomic signature of exosomes derived from the human cell lines normal colon mucosa (NCM460D), and colorectal cancer (CRC) nonmetastatic (HCT116) and metastatic (SW620), and exosomes isolated from the plasma of nonmetastatic and metastatic CRC patients and healthy donors. Analysis of this exhaustive lipid study highlighted changes in some molecular species that were found in the cell lines and confirmed in the patients. For example, exosomes from primary cancer patients and nonmetastatic cells compared with healthy donors and control cells displayed a common marked increase in phosphatidylcholine (PC) 34 : 1, phosphatidylethanolamine (PE) 36 : 2, sphingomyelin (SM) d18 : 1/16 : 0, hexosylceramide (HexCer) d18 : 1/24 : 0 and HexCer d18 : 1/24 : 1. Interestingly, these same lipids species were decreased in the metastatic cell line and patients. Further, levels of PE 34 : 2, PE 36 : 2, and phosphorylated PE p16 : 0/20 : 4 were also significantly decreased in metastatic conditions when compared to the nonmetastatic counterparts. The only molecule species found markedly increased in metastatic conditions (in both patients and cells) when compared to controls was ceramide (Cer) d18 : 1/24 : 1. These decreases in lipid species in the extracellular vesicles might reflect function‐associated changes in the metastatic cell membrane. Although these potential biomarkers need to be validated in a larger cohort, they provide new insight toward the use of clusters of lipid biomarkers rather than a single molecule for the diagnosis of different stages of CRC.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2710 - 2718"},"PeriodicalIF":6.6,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42618550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Ageing and cancer: a research gap to fill 衰老与癌症:有待填补的研究空白

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-05-03 DOI: 10.1002/1878-0261.13222

E. Solary, Nancy Abou-Zeid, F. Calvo

{"title":"Ageing and cancer: a research gap to fill","authors":"E. Solary, Nancy Abou-Zeid, F. Calvo","doi":"10.1002/1878-0261.13222","DOIUrl":"https://doi.org/10.1002/1878-0261.13222","url":null,"abstract":"The complex mechanisms of ageing biology are increasingly understood. Interventions to reduce or delay ageing‐associated diseases are emerging. Cancer is one of the diseases promoted by tissue ageing. A clockwise mutational signature is identified in many tumours. Ageing might be a modifiable cancer risk factor. To reduce the incidence of ageing‐related cancer and to detect the disease at earlier stages, we need to understand better the links between ageing and tumours. When a cancer is established, geriatric assessment and measures of biological age might help to generate evidence‐based therapeutic recommendations. In this approach, patients and caregivers would include the respective weight to give to the quality of life and survival in the therapeutic choices. The increasing burden of cancer in older patients requires new generations of researchers and geriatric oncologists to be trained, to properly address disease complexity in a multidisciplinary manner, and to reduce health inequities in this population of patients. In this review, we propose a series of research challenges to tackle in the next few years to better prevent, detect and treat cancer in older patients while preserving their quality of life.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3220 - 3237"},"PeriodicalIF":6.6,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46661638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5