Oncogenesis最新文献

{"title":"Retraction Note: A natural food sweetener with anti-pancreatic cancer properties.","authors":"C Liu, L-H Dai, D-Q Dou, L-Q Ma, Y-X Sun","doi":"10.1038/s41389-023-00461-7","DOIUrl":"https://doi.org/10.1038/s41389-023-00461-7","url":null,"abstract":"","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"15"},"PeriodicalIF":6.2,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9132955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: FAM83B inhibits ovarian cancer cisplatin resistance through inhibiting Wnt pathway.","authors":"Shanyang He, Wei Wang, Zhiyong Wan, Hongwei Shen, Yunhe Zhao, Zeshan You, Jun Liu, Liwen Zhu","doi":"10.1038/s41389-023-00459-1","DOIUrl":"https://doi.org/10.1038/s41389-023-00459-1","url":null,"abstract":"","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"14"},"PeriodicalIF":6.2,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9137644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of tripartite motif-containing 47 (TRIM47) confers sensitivity to PARP inhibition via ubiquitylation of BRCA1 in triple negative breast cancer cells.","authors":"Fengen Liu,&nbsp;Binhui Xie,&nbsp;Rong Ye,&nbsp;Yuankang Xie,&nbsp;Baiyin Zhong,&nbsp;Jinrong Zhu,&nbsp;Yao Tang,&nbsp;Zelong Lin,&nbsp;Huiru Tang,&nbsp;Ziqing Wu,&nbsp;Heping Li","doi":"10.1038/s41389-023-00453-7","DOIUrl":"https://doi.org/10.1038/s41389-023-00453-7","url":null,"abstract":"<p><p>Triple-negative breast cancers (TNBC) frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. However, less than 15% of TNBC patients were found to carry BRCA1 mutation, indicating that there are other mechanisms regulating BRCA1-deficient in TNBC. In the current study, we shown that overexpression of TRIM47 correlates with progression and poor prognosis in triple-negative breast cancer. Moreover, we demonstrated that TRIM47 directly interacts with BRCA1 and induces ubiquitin-ligase-mediated proteasome turnover of BRCA1, subsequently leads to a decrease of BRCA1 protein levels in TNBC. Moreover, the downstream gene expression of BRCA1, such as p53, p27, p21 was significantly reduced in the overexpression of TRIM47 cell lines but increased in TRIM47-deleted cells. Functionally, we found that overexpression of TRIM47 in TNBC cells confers an exquisite sensitivity to olaparib, an inhibitor of poly-(ADP-ribose)-polymerase (PARP), but TRIM47 inhibition significantly confers TNBC cells resistance to olaparib both in vitro and in vivo. Furthermore, we showed that overexpression of BRCA1 significant increase the olaparib resistance in TRIM47-overexpression-induced PARP inhibitions sensitivity. Taken together, our results uncover a novel mechanism for BRCA1-deficient in TNBC and targeting TRIM47/BRCA1 axis may be a promising prognostic factor and a valuable therapeutic target for TNBC.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"13"},"PeriodicalIF":6.2,"publicationDate":"2023-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9100602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP35 promotes cell proliferation and chemotherapeutic resistance through stabilizing FUCA1 in colorectal cancer.","authors":"Yi Xiao,&nbsp;Xiaoyu Jiang,&nbsp;Ke Yin,&nbsp;Tianshu Miao,&nbsp;Hanlin Lu,&nbsp;Wenqing Wang,&nbsp;Lijuan Ma,&nbsp;Yinghui Zhao,&nbsp;Chunyan Liu,&nbsp;Yun Qiao,&nbsp;Pengju Zhang","doi":"10.1038/s41389-023-00458-2","DOIUrl":"https://doi.org/10.1038/s41389-023-00458-2","url":null,"abstract":"<p><p>Ubiquitin-specific-processing proteases 35 (USP35) is an under-characterized deubiquitinase and its role in colorectal cancer (CRC) remains unclear. Here, we focus on delineating the impact of USP35 on CRC cell proliferation and chemo-resistance, as well as the possible regulatory mechanism. By examining the genomic database and clinical samples, we found that USP35 was overexpressed in CRC. Further functional studies showed that enhanced USP35 expression promoted CRC cell proliferation and resistance to oxaliplatin (OXA) and 5-fluorouracil (5-FU), whereas USP35 depletion impeded cell proliferation and sensitized cells to OXA and 5-FU treatments. Then, to explore the possible mechanism underlying USP35-triggered cellular responses, we performed co-immunoprecipitation (co-IP) followed by mass spectrometry (MS) analysis and identified α-L-fucosidase 1 (FUCA1) as a direct deubiquitiation target of USP35. Importantly, we demonstrated that FUCA1 was an essential mediator for USP35-induced cell proliferation and chemo-resistance in vitro and in vivo. Finally, we observed that nucleotide excision repair (NER) components (e.g., XPC, XPA, ERCC1) were up-regulated by USP35-FUCA1 axis, indicating a potential mechanism for USP35-FUCA1-mediated platinum resistance in CRC. Together, our results for the first time explored the role and important mechanism of USP35 in CRC cell proliferation and chemotherapeutic response, providing a rationale for USP35-FUCA1-targeted therapy in CRC.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"12"},"PeriodicalIF":6.2,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10828973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.","authors":"Gilles Rademaker,&nbsp;Brunella Costanza,&nbsp;Justine Bellier,&nbsp;Michael Herfs,&nbsp;Raphaël Peiffer,&nbsp;Ferman Agirman,&nbsp;Naïma Maloujahmoum,&nbsp;Yvette Habraken,&nbsp;Philippe Delvenne,&nbsp;Akeila Bellahcène,&nbsp;Vincent Castronovo,&nbsp;Olivier Peulen","doi":"10.1038/s41389-023-00455-5","DOIUrl":"https://doi.org/10.1038/s41389-023-00455-5","url":null,"abstract":"","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"11"},"PeriodicalIF":6.2,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10817617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients.","authors":"Simone De Fabritiis,&nbsp;Silvia Valentinuzzi,&nbsp;Gianluca Piras,&nbsp;Ilaria Cicalini,&nbsp;Damiana Pieragostino,&nbsp;Sara Pagotto,&nbsp;Silvia Perconti,&nbsp;Mirco Zucchelli,&nbsp;Alberto Schena,&nbsp;Elisa Taschin,&nbsp;Gloria Simona Berteşteanu,&nbsp;Diana Liberata Esposito,&nbsp;Antonio Stigliano,&nbsp;Vincenzo De Laurenzi,&nbsp;Francesca Schiavi,&nbsp;Mario Sanna,&nbsp;Piero Del Boccio,&nbsp;Fabio Verginelli,&nbsp;Renato Mariani-Costantini","doi":"10.1038/s41389-023-00456-4","DOIUrl":"https://doi.org/10.1038/s41389-023-00456-4","url":null,"abstract":"<p><p>Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2'-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"10"},"PeriodicalIF":6.2,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PELI1 and EGFR cooperate to promote breast cancer metastasis.","authors":"Jie Qi,&nbsp;Guangsen Xu,&nbsp;Xiaoxia Wu,&nbsp;Chunhua Lu,&nbsp;Yuemao Shen,&nbsp;Baobing Zhao","doi":"10.1038/s41389-023-00457-3","DOIUrl":"https://doi.org/10.1038/s41389-023-00457-3","url":null,"abstract":"<p><p>Pellino-1 (PELI1) is an E3 ubiquitin ligase acting as a key regulator for the inflammation and autoimmunity via the ubiquitination of the substrate proteins. There is increasing evidence to support that PELI1 functions as an oncoprotein in tumorigenesis and metastasis. However, the molecular mechanism underlying the high expression and oncogenic roles of PELI1 in cancers remains limited. Herein, we revealed a novel regulation mechanism by which PELI1 and EGFR cooperate to promote breast cancer metastasis. EGFR is positively correlated with PELI1 expression in breast cancers, and its activation led to the phosphorylation of PELI1 at Tyr154 and Thr264, which subsequently activated its E3 ubiquitin ligase. Simultaneously, PELI1 physically interacted with and enhanced the stability of EGFR via the K63-linked polyubiquitination in reverse. The co-inhibition of the PELI1-EGFR showed synergetic effect to repress breast cancer metastasis. Furthermore, we identified a compound S62 as a small molecule disruptor of PELI1/EGFR that effectively repressed breast cancer metastasis. Our study not only uncovered the emerging roles of PELI1/EGFR interaction in the progression of breast cancer, but also provided an effective strategy for the inhibition of metastasis in breast cancer.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"9"},"PeriodicalIF":6.2,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10788644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generating in vitro models of NTRK-fusion mesenchymal neoplasia as tools for investigating kinase oncogenic activation and response to targeted therapy.","authors":"Fabio Vanoli,&nbsp;Laurie Herviou,&nbsp;Yusuke Tsuda,&nbsp;Patricia Sung,&nbsp;Ziyu Xie,&nbsp;Eve Fishinevich,&nbsp;Soe S Min,&nbsp;William Mallen,&nbsp;Henry de Traux de Wardin,&nbsp;Yanming Zhang,&nbsp;Maria Jasin,&nbsp;Cristina R Antonescu","doi":"10.1038/s41389-023-00454-6","DOIUrl":"https://doi.org/10.1038/s41389-023-00454-6","url":null,"abstract":"<p><p>The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as pan-tumor oncogenic drivers has led to new personalized therapies in oncology. Recent studies investigating NTRK fusions among mesenchymal neoplasms have identified several emerging soft tissue tumor entities displaying various phenotypes and clinical behaviors. Among them, tumors resembling lipofibromatosis or malignant peripheral nerve sheath tumors often harbor intra-chromosomal NTRK1 rearrangements, while most infantile fibrosarcomas are characterized by canonical ETV6::NTRK3 fusions. However, appropriate cellular models to investigate mechanisms of how kinase oncogenic activation through gene fusions drives such a wide spectrum of morphology and malignancy are lacking. Progress in genome editing has facilitated the efficient generation of chromosomal translocations in isogenic cell lines. In this study we employ various strategies to model NTRK fusions, including LMNA::NTRK1 (interstitial deletion) and ETV6::NTRK3 (reciprocal translocation) in human embryonic stem (hES) cells and mesenchymal progenitors (hES-MP). Here, we undertake various methods to model non-reciprocal, intrachromosomal deletions/translocations by induction of DNA double strand breaks (DSBs) exploiting either the repair mechanisms of homology directed repair (HDR) or non-homologous end joining (NHEJ). Expression of LMNA::NTRK1 or ETV6::NTRK3 fusions in either hES cells or hES-MP did not affect cell proliferation. However, the level of mRNA expression of the fusion transcripts was significantly upregulated in hES-MP, and phosphorylation of the LMNA::NTRK1 fusion oncoprotein was noted only in hES-MP but not in hES cells. Similarly, an NTRK1-driven transcriptional profile related to neuronal and neuroectodermal lineage was upregulated mainly in hES-MP, supporting the importance of appropriate cellular context in modeling cancer relevant aberrations. As proof of concept of the validity of our in vitro models, phosphorylation was depleted by two TRK inhibitors, Entrectinib and Larotrectinib, currently used as targeted therapy for tumors with NTRK fusions.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"8"},"PeriodicalIF":6.2,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance.","authors":"Serena Diazzi,&nbsp;Sophie Tartare-Deckert,&nbsp;Marcel Deckert","doi":"10.1038/s41389-023-00452-8","DOIUrl":"https://doi.org/10.1038/s41389-023-00452-8","url":null,"abstract":"<p><p>Advanced cutaneous melanoma is the deadliest form of skin cancer and one of the most aggressive human cancers. Targeted therapies (TT) against BRAF mutated melanoma and immune checkpoints blockade therapies (ICB) have been a breakthrough in the treatment of metastatic melanoma. However, therapy-driven resistance remains a major hurdle in the clinical management of the metastatic disease. Besides shaping the tumor microenvironment, current treatments impact transition states to promote melanoma cell phenotypic plasticity and intratumor heterogeneity, which compromise treatment efficacy and clinical outcomes. In this context, mesenchymal-like dedifferentiated melanoma cells exhibit a remarkable ability to autonomously assemble their own extracellular matrix (ECM) and to biomechanically adapt in response to therapeutic insults, thereby fueling tumor relapse. Here, we review recent studies that highlight mechanical phenotypic plasticity of melanoma cells as a hallmark of adaptive and non-genetic resistance to treatment and emerging driver in cross-resistance to TT and ICB. We also discuss how targeting BRAF-mutant dedifferentiated cells and ECM-based mechanotransduction pathways may overcome melanoma cross-resistance.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"7"},"PeriodicalIF":6.2,"publicationDate":"2023-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negligible role of TRAIL death receptors in cell death upon endoplasmic reticulum stress in B-cell malignancies.","authors":"Francesca Favaro,&nbsp;Demi Both,&nbsp;Ingrid A M Derks,&nbsp;Marcel Spaargaren,&nbsp;Cristina Muñoz-Pinedo,&nbsp;Eric Eldering","doi":"10.1038/s41389-023-00450-w","DOIUrl":"https://doi.org/10.1038/s41389-023-00450-w","url":null,"abstract":"<p><p>Impairments in protein folding in the endoplasmic reticulum (ER) lead to a condition called ER stress, which can trigger apoptosis via the mitochondrial or the death receptor (extrinsic) pathway. There is controversy concerning involvement of the death receptor (DR)4 and DR5-Caspase-8 -Bid pathway in ER stress-mediated cell death, and this axis has not been fully studied in B-cell malignancies. Using three B-cell lines from Mantle Cell Lymphoma, Waldenström's macroglobulinemia and Multiple Myeloma origins, we engineered a set of CRISPR KOs of key components of these cell death pathways to address this controversy. We demonstrate that DR4 and/or DR5 are essential for killing via TRAIL, however, they were dispensable for ER-stress induced-cell death, by Thapsigargin, Brefeldin A or Bortezomib, as were Caspase-8 and Bid. In contrast, the deficiency of Bax and Bak fully protected from ER stressors. Caspase-8 and Bid were cleaved upon ER-stress stimulation, but this was DR4/5 independent and rather a result of mitochondrial-induced feedback loop subsequent to Bax/Bak activation. Finally, combined activation of the ER-stress and TRAIL cell-death pathways was synergistic with putative clinical relevance for B-cell malignancies.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"6"},"PeriodicalIF":6.2,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10681096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}