Molecular Oncology最新文献

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Imperial strategy of cancer cells through mitochondrial transfer. 通过线粒体转移癌细胞的帝国策略。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-05 DOI: 10.1002/1878-0261.70142
Takamasa Ishino, Yosuke Togashi
{"title":"Imperial strategy of cancer cells through mitochondrial transfer.","authors":"Takamasa Ishino, Yosuke Togashi","doi":"10.1002/1878-0261.70142","DOIUrl":"https://doi.org/10.1002/1878-0261.70142","url":null,"abstract":"<p><p>Mitochondria are essential organelles that regulate various biological processes including metabolism. Beyond their intracellular functions, intercellular mitochondrial transfer has emerged as a novel mechanism of intercellular communication. Notably, an increasing number of studies have reported its occurrence in the tumor microenvironment (TME), where it contributes to tumor progression. While previous studies largely characterized cancer cells as recipients of mitochondria, Cangkrama et al. demonstrated that cancer cells donate their mitochondria to fibroblasts via tunneling nanotubes. The mitochondrial transfer to fibroblasts reprogrammed them into cancer-associated fibroblasts exhibiting combined myofibroblastic and inflammatory characteristics, with enhanced oxidative metabolism and pro-tumorigenic activity. Our group has identified mitochondrial 'hijack' from cancer cells to tumor-infiltrating lymphocytes, leading to an impaired antitumor immunity. These insights underscore the need to recognize cancer cells as mitochondrial donors in the TME capable of reshaping the TME to their own advantage, resembling a dynastic expansion strategy that exerts influence by strategically placing lineages.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228641","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: 0
Characterizing epithelial-mesenchymal transition-linked heterogeneity in breast cancer circulating tumor cells at a single-cell level. 在单细胞水平上表征乳腺癌循环肿瘤细胞上皮-间质过渡相关的异质性。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-05 DOI: 10.1002/1878-0261.70132
Justyna Topa, Julia Richert, Tomasz Stokowy, Alicja Staśczak, Mariusz Szajewski, Maciej Ciesielski, Petra M Grešner, Bartłomiej Tomasik, Łukasz Arcimowicz, Agnieszka Stankiewicz, Grażyna Suchodolska, Elżbieta Senkus, Wiesław Kruszewski, Anna J Żaczek, Aleksandra Markiewicz
{"title":"Characterizing epithelial-mesenchymal transition-linked heterogeneity in breast cancer circulating tumor cells at a single-cell level.","authors":"Justyna Topa, Julia Richert, Tomasz Stokowy, Alicja Staśczak, Mariusz Szajewski, Maciej Ciesielski, Petra M Grešner, Bartłomiej Tomasik, Łukasz Arcimowicz, Agnieszka Stankiewicz, Grażyna Suchodolska, Elżbieta Senkus, Wiesław Kruszewski, Anna J Żaczek, Aleksandra Markiewicz","doi":"10.1002/1878-0261.70132","DOIUrl":"https://doi.org/10.1002/1878-0261.70132","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) generates heterogeneity in circulating tumor cells (CTCs), affecting their biological properties and hampering their detection. This limits our understanding of the mechanisms underlying hematogenous dissemination, especially in early breast cancer (BC), where CTCs are rare. Here, we aimed to detect CTCs with different EMT statuses from BC patients. CTCs in blood samples from 107 BC patients were evaluated using immunomagnetic depletion and multi-marker immunofluorescence (EpCAM, E-cadherin, MCAM, cell surface vimentin, CD31, CD45), followed by single-cell transcriptomics. CTCs were detected in 51.9% of therapy-naïve early BC cases, with 3.8% showing only epithelial CTCs (eCTCs), 5.8% epithelial-mesenchymal (emCTCs), 26.0% mesenchymal (mCTCs), and 16.3% mixed phenotypes. CTC heterogeneity was more frequent in triple-negative (86%) than in luminal BC (17%, P = 0.008). Lymph node involvement strongly predicted dissemination of all CTC phenotypes, while tumor size correlated with mCTC abundance. Single-cell RNA sequencing revealed downregulation of ribosomal genes and translation inhibition in CTCs with mesenchymal features, linked to mTORC1 signaling. Findings were also validated in an independent dataset, highlighting vulnerabilities in CTCs during dissemination.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228674","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: 0
The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy. 神经嵴相关基因ERRFI1参与黑色素瘤的进展和对靶向治疗的耐药性。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-03 DOI: 10.1002/1878-0261.70137
Nina Wang, Qian Sun, Daniel Novak, Lei Zhu, Juliane Poelchen, Tamara Steinfass, Yiman Wang, Viktor Umansky, Jochen Utikal
{"title":"The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.","authors":"Nina Wang, Qian Sun, Daniel Novak, Lei Zhu, Juliane Poelchen, Tamara Steinfass, Yiman Wang, Viktor Umansky, Jochen Utikal","doi":"10.1002/1878-0261.70137","DOIUrl":"https://doi.org/10.1002/1878-0261.70137","url":null,"abstract":"<p><p>Targeted therapy has been established as a therapeutic option for the treatment of metastatic melanoma. Despite initially being very efficient, many tumors develop resistance to targeted therapy, leading to its failure. We previously demonstrated that the neural crest (NC)-associated gene ERRFI1 is highly expressed in metastatic melanoma and correlates with a bad prognosis. Here, we show that the expression of ERRFI1 was upregulated in melanoma and negatively correlated with the expression of melanocytic differentiation markers, such as MITF and TYR. Downregulation of ERRFI1 with the help of siRNA increased the susceptibility of melanoma cells toward BRAF inhibition (BRAFi) and resensitized BRAFi-resistant melanoma cells to BRAFi. Mass spectrometry-based proteomic analysis revealed that ERRFI1 silencing diminished the activation of the mitogen-activated protein kinase (MAPK) and AKT signaling pathways, which usually contribute to drug resistance. Furthermore, we show that miR-200c targeted the 3'UTR of ERRFI1 and reduced its expression, resulting in the resensitization of BRAFi-resistant melanoma cells to BRAFi. Our study results suggest that ERRFI1 could be a potential therapeutic target for the treatment of metastatic melanoma.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225478","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: 0
Cell-free DNA aneuploidy score as a dynamic early response marker in prostate cancer. 作为前列腺癌早期反应动态标记物的无细胞 DNA 非整倍体评分
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-03-14 DOI: 10.1002/1878-0261.13797
Khrystany T Isebia, Anouk C de Jong, Lisanne F van Dessel, Vanja de Weerd, Corine Beaufort, Jean Helmijr, José Alberto Nakauma-González, Job van Riet, Paul Hamberg, Daniel Vis, Michiel S van der Heijden, Nick Beije, Martijn P Lolkema, Teoman Deger, Saskia M Wilting, Ronald de Wit, Maurice P H M Jansen, John W M Martens
{"title":"Cell-free DNA aneuploidy score as a dynamic early response marker in prostate cancer.","authors":"Khrystany T Isebia, Anouk C de Jong, Lisanne F van Dessel, Vanja de Weerd, Corine Beaufort, Jean Helmijr, José Alberto Nakauma-González, Job van Riet, Paul Hamberg, Daniel Vis, Michiel S van der Heijden, Nick Beije, Martijn P Lolkema, Teoman Deger, Saskia M Wilting, Ronald de Wit, Maurice P H M Jansen, John W M Martens","doi":"10.1002/1878-0261.13797","DOIUrl":"10.1002/1878-0261.13797","url":null,"abstract":"<p><p>Cell-free circulating tumor DNA (ctDNA) has emerged as a promising biomarker for response evaluation in metastatic castration-resistant prostate cancer (mCRPC). The current study evaluated the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), a quick, tumor-agnostic and affordable ctDNA assay that requires a small input of DNA, to generate a genome-wide aneuploidy (GWA) score in mCRPC patients, and correlated this to matched metastatic tumor biopsies. In this prospective multicenter study, GWA scores were evaluated from blood samples of 196 mCRPC patients prior to treatment (baseline) with taxanes (docetaxel and cabazitaxel) and androgen receptor signaling inhibitors (ARSI; abiraterone and enzalutamide), and from 74 mCRPC patients at an early timepoint during treatment (early timepoint; median 21 days). Z-scores per chromosome arm were tested for their association with tumor tissue genomic alterations. We found that a high tumor load in blood (GWA<sup>high</sup>) at baseline was associated with poor response to ARSI [HR: 2.63 (95% CI: 1.86-3.72) P < 0.001] but not to taxanes. Interestingly, GWA<sup>high</sup> score at the early timepoint was associated with poor response to both ARSIs [HR: 6.73 (95% CI: 2.60-17.42) P < 0.001] and taxanes [2.79 (95% CI: 1.34-5.78) P = 0.006]. A significant interaction in Cox proportional hazards analyses was seen when combining GWA status and type of treatment (at baseline P = 0.008; early timepoint P = 0.018). In summary, detection of ctDNA in blood by mFast-SeqS is cheap, fast and feasible, and could be used at different timepoints as a potential predictor for outcome to ARSI and taxane treatment in mCRPC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2822-2832"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625323","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}
引用次数: 0
Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model. 在小鼠异种移植模型中,靶向 AKT/mTOR 通路可减轻结直肠癌循环肿瘤细胞的转移潜力。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-03-25 DOI: 10.1002/1878-0261.70024
Daniel J Smit, Thais Pereira-Veiga, Helena Brauer, Michael Horn, Paula Nissen, Thomas Mair, Bente Siebels, Hannah Voß, Ruimeng Zhuang, Marie-Therese Haider, Desiree Loreth, Margarita Iskhakova, Bele Lindemann, Julian Kött, Laure Cayrefourcq, Jasmin Wellbrock, Hartmut Schlüter, Klaus Pantel, Catherine Alix-Panabières, Manfred Jücker
{"title":"Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model.","authors":"Daniel J Smit, Thais Pereira-Veiga, Helena Brauer, Michael Horn, Paula Nissen, Thomas Mair, Bente Siebels, Hannah Voß, Ruimeng Zhuang, Marie-Therese Haider, Desiree Loreth, Margarita Iskhakova, Bele Lindemann, Julian Kött, Laure Cayrefourcq, Jasmin Wellbrock, Hartmut Schlüter, Klaus Pantel, Catherine Alix-Panabières, Manfred Jücker","doi":"10.1002/1878-0261.70024","DOIUrl":"10.1002/1878-0261.70024","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) play an important role in metastasis formation. Aberrant signaling of oncogenic pathways (e.g., PI3K/AKT/mTOR pathway) drives tumor progression. In this work, the susceptibility of the colon cancer CTC-derived cell line CTC-MCC-41 to AKT and mammalian target of rapamycin (mTOR) inhibitors was evaluated. Additionally, the functional role of the expressed AKT isoforms was characterized in this cell line. The efficacy of the AKT inhibitor MK2206, the mTOR inhibitor RAD001, and the combination was examined in CTC-MCC-41 cells in a murine intracardiac xenotransplantation model. Furthermore, stable isoform-specific AKT1 or AKT2 knockdowns (KDs) as well as AKT1/AKT2 double-KD cells were generated. Differentially regulated proteins and phospho-peptides were identified using liquid chromatography coupled mass spectrometry (LC-MS). CTC-MCC-41 cells showed a high susceptibility for dual targeting of AKT and mTOR in vivo, indicating that selective eradication of CTCs by AKT/mTOR inhibitors may be considered a new treatment option in cancer. KD of AKT1 or AKT2 significantly reduced the proliferation of CTC-MCC-41 cells. AKT KDs share commonly regulated proteins and phospho-proteins, but also regulate a large number uniquely. AKT1/AKT2 double-KD cells show a strongly dysregulated replication machinery, as well as a decrease in cell cycle activity and stem-cell-associated processes, underlining the non-redundant role of AKT isoforms.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2882-2904"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701066","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}
引用次数: 0
Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer. 一种靶向趋化因子受体CCR9的新型人源化单克隆抗体在胰腺癌中的治疗应用。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-05-28 DOI: 10.1002/1878-0261.70062
Hannah G McDonald, Anna M Reagan, Charles J Bailey, Mei Gao, Muqiang Gao, Angelica L Solomon, Michael J Cavnar, Prakash K Pandalai, Mautin T Barry-Hundeyin, Megan M Harper, Justin A Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim
{"title":"Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer.","authors":"Hannah G McDonald, Anna M Reagan, Charles J Bailey, Mei Gao, Muqiang Gao, Angelica L Solomon, Michael J Cavnar, Prakash K Pandalai, Mautin T Barry-Hundeyin, Megan M Harper, Justin A Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim","doi":"10.1002/1878-0261.70062","DOIUrl":"10.1002/1878-0261.70062","url":null,"abstract":"<p><p>The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C-C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 cells, NK cell-mediated cytotoxicity was promoted by SRB2. Dose-dependent SRB2 cytotoxicity was observed in PDAC PDOs. In patient-derived xenograft mouse models, cytotoxicity of SRB2 monotherapy and in combination with oxaliplatin was also shown. In humanized immune-competent mouse models, SRB2 efficacy was similar to other drugs, but two mice in this cohort had complete tumor regression. Our current studies suggest that therapeutic targeting of CCR9 may improve PDAC outcomes, and additional studies are underway to evaluate SRB2 for clinical use.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2978-2988"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174177","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}
引用次数: 0
Only the strong survive: therapeutic selective pressure drives medulloblastoma leptomeningeal metastasis. 只有强者才能生存:治疗选择性压力驱动成神经管细胞瘤轻脑膜转移。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-09-16 DOI: 10.1002/1878-0261.70125
Francis Y He, Adrienne Boire
{"title":"Only the strong survive: therapeutic selective pressure drives medulloblastoma leptomeningeal metastasis.","authors":"Francis Y He, Adrienne Boire","doi":"10.1002/1878-0261.70125","DOIUrl":"10.1002/1878-0261.70125","url":null,"abstract":"<p><p>Medulloblastoma (MB) is the most common malignant tumor in the central nervous system in childhood and regularly metastasizes to the leptomeninges following radiation therapy. Using patient-derived medulloblastoma models and genetically engineered mouse models, Nör et al. observed enhanced inflammation and infiltration of myeloid cells within the brain following irradiation. The authors identified inflammatory cytokines and the resulting breakdown of blood-brain barriers as the main culprits of MB leptomeningeal metastasis. This study demonstrated that targeting inflammation through the use of dexamethasone effectively reduced systemic inflammatory cytokines and the resulting radiation-induced leptomeningeal metastasis.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2761-2763"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075691","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}
引用次数: 0
ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling. ShcD 适应蛋白通过表皮生长因子受体信号的异常激活驱动三阴性乳腺癌细胞的侵袭。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-03-28 DOI: 10.1002/1878-0261.70022
Hayley R Lau, Hayley S Smith, Begüm Alural, Claire E Martin, Laura A New, Manali Tilak, Sara L Banerjee, Hannah N Robeson, Nicolas Bisson, Anne-Claude Gingras, Jasmin Lalonde, Nina Jones
{"title":"ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling.","authors":"Hayley R Lau, Hayley S Smith, Begüm Alural, Claire E Martin, Laura A New, Manali Tilak, Sara L Banerjee, Hannah N Robeson, Nicolas Bisson, Anne-Claude Gingras, Jasmin Lalonde, Nina Jones","doi":"10.1002/1878-0261.70022","DOIUrl":"10.1002/1878-0261.70022","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is highly metastatic and presents clinical challenges given the lack of targeted therapies. Here, we report that the ShcD phosphotyrosine adaptor protein is upregulated in TNBC, and its expression correlates with overall reduced patient survival and decreased response to chemotherapy. In human breast cancer cells, we demonstrate that ShcD expression promotes cell invasion and reduces adhesion, and that these effects are abrogated by mutating the ShcD phosphotyrosine binding (PTB) domain. Similarly, in a three-dimensional assembloid model, ShcD-expressing spheroids derived from brain metastatic TNBC cells show enhanced infiltration into cerebral organoids. Using a proteomic screen for ShcD binding partners, we identify multiple components of epidermal growth factor receptor (EGFR) signaling and confirm these interactions with ShcD but not the PTB mutant. Interestingly, the ShcD interactome correlates with EGFR tyrosine kinase inhibitor resistance, in line with our findings that ShcD overexpression results in hyperphosphorylation of EGFR while ShcD knockout or PTB mutation reverts this response. Lastly, pharmacological inhibition of the ShcD PTB domain using indomethacin in TNBC cells decreases EGFR binding and hyperphosphorylation and reduces cell invasion. Altogether, our results identify ShcD as a potential contributor to metastasis in TNBC, and they provide a molecular basis for clinical targeting of adaptor proteins.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2833-2859"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730501","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}
引用次数: 0
Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles. 早期转移的特点是Gr1+细胞失调,并被免疫调节纳米颗粒抑制。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-04-23 DOI: 10.1002/1878-0261.70040
Jeffrey A Ma, Sophia M Orbach, Kate V Griffin, Kathryn Kang, Yining Zhang, Rebecca S Pereles, Ian A Schrack, Guillermo Escalona, Jacqueline S Jeruss, Lonnie D Shea
{"title":"Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles.","authors":"Jeffrey A Ma, Sophia M Orbach, Kate V Griffin, Kathryn Kang, Yining Zhang, Rebecca S Pereles, Ian A Schrack, Guillermo Escalona, Jacqueline S Jeruss, Lonnie D Shea","doi":"10.1002/1878-0261.70040","DOIUrl":"10.1002/1878-0261.70040","url":null,"abstract":"<p><p>Cancer metastasis is supported by dysregulated myeloid-derived suppressor cells, but myeloid cells are highly heterogeneous populations with distinct subsets that may support or inhibit tumor cell colonization. We hypothesize that Gr1+ myeloid cells transform in phenotype to support tumor cell colonization at the metastatic niche. In the 4T1 model of metastatic breast cancer, we investigate changes in the composition and phenotype of Gr1+ cells between premetastatic disease and early metastasis. Gr1+ cells in the lung were found to transition towards immunosuppressive and tumor-supportive phenotypes with disease progression. While the composition of myeloid cells becomes dysregulated systemically, cells in the blood do not develop tumor-supportive phenotypes, indicating that protumor functions are specific to the lung. In vitro assays demonstrate that Gr1+ cells from early metastatic lungs support tumor cell survival, migration, and proliferation, which is linked to chitinase-3-like protein 1 (CHI3L1) signaling. The intravenous injection of polymeric nanoparticles reprograms Gr1+ cell phenotypes, reduces the secretion of CHI3L1, and inhibits metastasis. These findings indicate that dysregulated Gr1+ cells are a therapeutic target for early metastasis and can be targeted with polymeric nanoparticles.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2860-2881"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030031","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}
引用次数: 0
Highly multiplexed digital PCR assay for simultaneous quantification of variant allele frequencies and copy number alterations of KRAS and GNAS in pancreatic cancer precursors. 用于同时定量胰腺癌前体KRAS和GNAS变异等位基因频率和拷贝数变化的高度多重数字PCR方法。
IF 4.5 2区 医学
Molecular Oncology Pub Date : 2025-10-01 Epub Date: 2025-03-12 DOI: 10.1002/1878-0261.70011
Junko Tanaka, Tatsuo Nakagawa, Yusuke Ono, Yoshio Kamura, Takeshi Ishida, Hidemasa Kawabata, Kenji Takahashi, Hiroki Sato, Andrew S Liss, Yusuke Mizukami, Takahide Yokoi
{"title":"Highly multiplexed digital PCR assay for simultaneous quantification of variant allele frequencies and copy number alterations of KRAS and GNAS in pancreatic cancer precursors.","authors":"Junko Tanaka, Tatsuo Nakagawa, Yusuke Ono, Yoshio Kamura, Takeshi Ishida, Hidemasa Kawabata, Kenji Takahashi, Hiroki Sato, Andrew S Liss, Yusuke Mizukami, Takahide Yokoi","doi":"10.1002/1878-0261.70011","DOIUrl":"10.1002/1878-0261.70011","url":null,"abstract":"<p><p>Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursor lesions. Detecting these precursors and monitoring their progression are crucial for early PDAC diagnosis. Digital PCR (dPCR) is a highly sensitive nucleic acid quantification technique and offers a cost-effective option for patient follow-up. However, the clinical utility of conventional dPCR is restricted by multiplexing constraints, particularly due to the challenge of simultaneously quantifying multiple mutations and amplifications. In this study, we applied highly multiplexed dPCR and melting curve analysis to simultaneously measure single nucleotide mutations and amplifications of KRAS and GNAS. The developed 14-plex assay included both wild-type and mutant KRAS, a common driver gene in both PanIN and IPMN, and GNAS, which is specifically mutated in IPMN, along with RPP30, a reference gene for copy number alterations (CNAs). This multiplex dPCR method detected all target mutations with a limit of detection below 0.2% while quantifying CNAs. Additionally, the assay accurately quantified variant allele frequencies in liquid biopsy and tissue samples from both pancreatic neoplasm precursor and PDAC patients, indicating its potential for use in comprehensive patient follow-up.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2921-2935"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616140","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}
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