Molecular Cancer Research最新文献

{"title":"CGPA: A Multicontext Cancer Gene Prognosis Atlas.","authors":"Biwei Cao, Xiaoqing Yu, Guillermo Gonzalez, Amith R Murthy, Tingyi Li, Yuanyuan Shen, Sijie Yao, Xuefeng Wang","doi":"10.1158/1541-7786.MCR-24-1186","DOIUrl":"10.1158/1541-7786.MCR-24-1186","url":null,"abstract":"<p><p>Cancer transcriptomic data are widely leveraged to evaluate the prognostic relevance of targeted genes. However, most basic and translational studies continue to rely on univariable survival analysis, which often fails to capture the full prognostic potential of genes or account for their biological context. Recognizing the complexity of revealing multifaceted prognostic effects, especially when incorporating covariates and variable thresholds, we present the Cancer Gene Prognosis Atlas (CGPA), an interactive tool specifically designed for basic and molecular cancer researchers. CGPA provides an intuitive, user-friendly interface that enables in-depth, customizable prognostic analysis across cancer types. Beyond single-gene analyses, it supports data-driven exploration of gene pairs and gene-hallmark relationships, providing insights into key mechanisms such as synthetic lethality and immunosuppression. CGPA further extends its capabilities to assess multigene panels using both public and user-provided data and includes a dedicated portal for cancer immunotherapy datasets. Collectively, CGPA's comprehensive yet user-friendly toolkit enables researchers to interrogate the prognostic landscape of genes with precision, tailor analyses to specific biological hypotheses, and accelerate biomarker discovery and validation through the integration of both mechanisticically-informed and data-driven approaches.</p><p><strong>Implications: </strong>CGPA is a streamlined, interactive platform for multicontext gene-centric prognostic analysis, simplifying biomarker discovery and validation for molecular and basic cancer scientists and bridging a critical gap in translational cancer research.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"188-197"},"PeriodicalIF":5.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959965","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":"BCOR Mutations Deregulate Cell Cycle and Hypoxic Adaptation Pathways in Retinoblastoma.","authors":"Michelle G Zhang, Jeffim N Kuznetsoff, Natalie C Cetta, Sebastian Salazar, Renata L Volonterio, Stefan Kurtenbach, Zelia M Correa, Daniel Pelaez, J William Harbour","doi":"10.1158/1541-7786.MCR-24-1078","DOIUrl":"10.1158/1541-7786.MCR-24-1078","url":null,"abstract":"<p><p>Retinoblastoma is the most common pediatric eye cancer. Most cases of retinoblastoma are initiated by biallelic mutational inactivation of the RB1 gene, yet most retinoblastoma tumors harbor additional genomic aberrations that may promote tumor progression. After RB1, the gene that is most commonly mutated gene in retinoblastoma is BCOR, which is mutated in approximately 20% of retinoblastoma tumors and is associated with a more aggressive tumor phenotype and worse patient outcomes. Despite its importance, little is known about the role of BCOR in retinoblastoma. In this study, we interrogated BCOR in low-passage retinoblastoma cell lines using mass spectrometry, chromatin immunoprecipitation sequencing, and RNA sequencing. We show that the BCOR protein interacts with members of the noncanonical polycomb repressive complex 1.1 and localizes at gene loci with traditionally activating and repressing chromatin markers. Loss of BCOR downregulates the expression of genes associated with cell-cycle regulation and upregulates genes associated with hypoxic adaptation. We conclude that BCOR mutations slow cell proliferation and drive hypoxic adaptation in retinoblastoma via epigenetic mechanisms that may be amenable to targeted therapy.</p><p><strong>Implications: </strong>This study reveals that BCOR may play a noncanonical, multifaceted role in retinoblastoma with implications in cell cycle, differentiation, and hypoxic adaptation, ultimately shedding insight into its molecular framework for future therapeutic strategies.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"179-187"},"PeriodicalIF":5.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452448","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":"SMARCA4 Loss Promotes Late-Stage Tumor Progression in Nonneuroendocrine Small Cell Lung Cancer.","authors":"Nicole A Kirk, Jin Ng, Kate-Lin Ly, Miae Choi, Young Ho Ban, Godfrey A Dzhivhuho, Jinho Jang, Kyung-Pil Ko, Michael S Kareta, Jae-Il Park, Anthony N Karnezis, Anish Thomas, Kate D Sutherland, Kwon-Sik Park","doi":"10.1158/1541-7786.MCR-25-0592","DOIUrl":"10.1158/1541-7786.MCR-25-0592","url":null,"abstract":"<p><p>The role of SMARCA4, a core component of the SWI/SNF chromatin remodeling complex, remains unclear in small cell lung cancer (SCLC). Using genetically engineered mouse models, we found that SMARCA4 deletion markedly reduced tumor formation and decreased expression of ASCL1, a key neuroendocrine lineage factor. However, SMARCA4-deficient tumors, although smaller, exhibited aggressive features, including variant histology and loss of neuroendocrine differentiation. In established tumor cells, SMARCA4 knockdown did not affect proliferation in vitro but unexpectedly promoted tumor growth in vivo, accompanied by reduced expression and cell surface display of polio virus receptor, a ligand critical for T- and NK-cell activation. Although the contribution of these immune cells to SMARCA4 tumor suppressor activity remains unknown, these findings suggest distinct roles of SMARCA4 in promoting early tumor development but restraining progression of late-stage, neuroendocrine-low tumors.</p><p><strong>Implications: </strong>This study underscores the importance of tumor context and timing in understanding and targeting SMARCA4 and other chromatin regulators in SCLC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"169-178"},"PeriodicalIF":5.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900756","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":"Expression of Concern: FOXM1 Confers Acquired Cisplatin Resistance in Breast Cancer Cells.","authors":"Jimmy M-M Kwok, Barrie Peck, Lara J Monteiro, Helma D C Schwenen, Julie Millour, R Charles Coombes, Stephen S Myatt, Eric W-F Lam","doi":"10.1158/1541-7786.MCR-26-0060","DOIUrl":"10.1158/1541-7786.MCR-26-0060","url":null,"abstract":"","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":"24 3","pages":"200"},"PeriodicalIF":4.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344834","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}

{"title":"Expression of Concern: The p38 MAPK-MK2 Axis Regulates E2F1 and FOXM1 Expression after Epirubicin Treatment.","authors":"Natalia de Olano, Chuay-Yeng Koo, Lara J Monteiro, Paola H Pinto, Ana R Gomes, Rosa Aligue, Eric W-F Lam","doi":"10.1158/1541-7786.MCR-26-0061","DOIUrl":"10.1158/1541-7786.MCR-26-0061","url":null,"abstract":"","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":"24 3","pages":"199"},"PeriodicalIF":4.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344808","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}

{"title":"The Multifaceted Role of Androgen Receptor Signaling in Immunity: Implications for Oncology.","authors":"Patrick Lee, Peter S Nelson","doi":"10.1158/1541-7786.MCR-25-0802","DOIUrl":"10.1158/1541-7786.MCR-25-0802","url":null,"abstract":"<p><p>Whereas the androgen receptor (AR) is canonically known for its role in the prostate and testis, AR signaling exerts broad immunomodulatory effects through direct and indirect signaling in multiple immune cell compartments and contributes significantly to sex differences in autoimmunity, infection, and cancer. Mouse model perturbations of androgen signaling through castration, testicular feminization, and cell type-specific Ar knockout have provided important insights into cell-intrinsic and -extrinsic mechanisms by which AR signaling affects innate and adaptive immunity. However, the precise molecular underpinnings of these effects remain largely unknown. Moreover, despite convincing epidemiologic and correlative observations that highlight the importance of AR signaling in human immune function, it remains unclear how reliably findings in mice will translate to humans. A better understanding of how to augment immune function through androgen signaling modulation could have significant clinical relevance for the treatment of cancer, as well as other disease states involving immune dysregulation. In this review, we discuss the current evidence for the functional effects of AR signaling within the major immune cell compartments of the innate and adaptive immune systems. We also review ongoing clinical efforts that modify AR signaling for the purpose of enhancing antitumor immunity.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"155-168"},"PeriodicalIF":5.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757089","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":"Synergistic DBNDD1-GDF15 Signaling Activates the NF-κB Pathway to Promote Colorectal Cancer Progression.","authors":"Xiaomin Qi, Caijuan Bai, Li Dong, Anqi Wang, Chaojun Wei, Yonghong Li, Mengyuan Zhao, Chongge You","doi":"10.1158/1541-7786.MCR-25-0153","DOIUrl":"10.1158/1541-7786.MCR-25-0153","url":null,"abstract":"<p><p>Colorectal cancer is a highly lethal gastrointestinal tract malignancy whose pathogenesis and molecular drivers are not fully understood. This study focused on searching for genes that are differentially expressed in cancer versus normal mucosa, with the goal of identifying molecular patterns of expression that are mechanistically linked to colorectal cancer pathogenesis. We analyzed 585 colorectal cancer samples and 329 normal samples from the Gene Expression Omnibus database, creating a weighted gene coexpression network analysis across 24,069 genes. Through this approach, five modules associated with colorectal cancer were identified, which were enriched in MAPK signaling and cholesterol metabolism pathways. Using least absolute shrinkage and selection operator (LASSO) regression, we selected 13 hub genes [ABCB5, AOC1, ARHGAP44, CACNG3, dysbindin domain-containing protein 1 (DBNDD1), GAS7, GTF2IRD1, PRSS22, SCN4A, TTC22, DLX6, PDK4, and SLC13A2] from these modules. Survival analysis indicated that higher expression of DBNDD1 correlated with worse overall survival in patients with colorectal cancer. Machine learning validation confirmed the stability of these genetic markers. Experimental validation demonstrated increased levels of DBNDD1 and growth differentiation factor 15 (GDF15) in colorectal cancer, promoting constant NF-κB (RELA) activation via DBNDD1-dependent GDF15 induction. Knocking down DBNDD1 inhibited cell proliferation, migration, and invasion in vitro (DLD1/HCT116 cells), alongside decreased GDF15 expression and reduced p-NF-κB p65-p-I-κB signaling. Additionally, DBNDD1 knockdown resulted in reduced tumor growth in vivo, highlighting that the DBNDD1-GDF15-NF-κB signaling pathway drives colorectal cancer pathogenesis.</p><p><strong>Implications: </strong>This study highlights the crucial role of the DBNDD1-GDF15-NF-κB signaling pathway in colorectal cancer development, positioning DBNDD1 as a promising target for precision medicine strategies aimed at enhancing patient outcomes.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"119-133"},"PeriodicalIF":4.7,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438425","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}

{"title":"Correction: p53 Frameshift Mutations Couple Loss-of-Function with Unique Neomorphic Activities.","authors":"David R Tong, Wen Zhou, Chen Katz, Kausik Regunath, Divya Venkatesh, Chinyere Ihuegbu, James J Manfredi, Oleg Laptenko, Carol Prives","doi":"10.1158/1541-7786.MCR-26-0033","DOIUrl":"https://doi.org/10.1158/1541-7786.MCR-26-0033","url":null,"abstract":"","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":"24 2","pages":"147"},"PeriodicalIF":4.7,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125916","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}

{"title":"Bone Metastatic Progression of Prostate Cancer Is Regulated by TRIM28-LDHA-Mediated Metabolism.","authors":"Miyeong Kim, Han Cong, Ryan Goettl, Jinpeng Liu, Ka-Wing Fong","doi":"10.1158/1541-7786.MCR-25-0676","DOIUrl":"10.1158/1541-7786.MCR-25-0676","url":null,"abstract":"<p><p>Castration-resistant prostate cancer, an advanced stage of prostate cancer, often leads to fatal bone metastasis. The vast majority of patients with prostate cancer who present with bone metastases suffer from bone lesions and other complications. Androgen receptor inhibitors, although improved, lack curative efficacy, necessitating an urgent demand for the development of innovative therapeutic strategies. TRIM28, also known as Krüppel-associated box-associated protein 1, is a transcription factor regulated by site-specific phosphorylation. Our recent study demonstrated that p90 ribosomal S6 kinase 1 is the protein kinase that directly phosphorylates TRIM28 at S473; as such, pS473-TRIM28 promotes the transcriptional activation of its gene targets. In this study, we reveal that TRIM28-S473 phosphorylation is readily detected in castration-resistant prostate cancer bone metastases, which is consistent with the previous report that p90 ribosomal S6 kinase is activated in prostate cancer bone metastases. Using bioinformatic and genomic analyses, we uncovered that lactate dehydrogenase A (LDHA) is a novel TRIM28-induced gene in bone metastatic prostate cancer. TRIM28 promotes the transcriptional activation of LDHA in a pS473-TRIM28-dependent manner. As such, TRIM28 is involved in LDH-related activities including lactate production and glycolysis. We also demonstrate that the TRIM28-LDHA axis is required for prostate tumor progression using an orthotopic bone injection model. Lastly, the application of an LDH inhibitor mitigates prostate cancer development in the bone. In summary, our study reveals an important role of the TRIM28-LDHA axis in prostate cancer progression in the bone, which may be targeted to mitigate the disease in the metastasis stage.</p><p><strong>Implications: </strong>TRIM28 upregulates LDHA and glycolysis, propelling prostate tumors in the bone; pharmacologic LDH blockade mitigates disease.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"93-105"},"PeriodicalIF":5.8,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308513","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":"PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.","authors":"Taylor Marohl, Kristen A Atkins, Lixin Wang, Kevin A Janes","doi":"10.1158/1541-7786.MCR-25-0211","DOIUrl":"10.1158/1541-7786.MCR-25-0211","url":null,"abstract":"<p><p>The most widely used cell line for studying ductal carcinoma in situ (DCIS) premalignancy is the transformed breast epithelial cell line, MCF10DCIS.com. During its original clonal isolation and selection, MCF10DCIS.com acquired a heterozygous M452I mutation in the proprotein convertase PCSK5, which has never been reported in any human cancer. The mutation is noteworthy because PCSK5 matures GDF11, a TGFβ superfamily ligand that suppresses progression of triple-negative breast cancer. We asked here whether PCSK5M452I and its activity toward GDF11 might contribute to the unique properties of MCF10DCIS.com. Using an optimized in-cell GDF11 maturation assay, we found that overexpressed PCSK5M452I was measurably active but at a fraction of the wild-type enzyme. In a PCSK5-/- clone of MCF10DCIS.com reconstituted with different PCSK5 alleles, PCSK5M452I was mildly defective in anterograde transport. However, the multicellular organization of PCSK5M452I addback cells in three-dimensional Matrigel cultures was significantly less circumscribed than wild-type and indistinguishable from a PCSK5T288P-null allele. Growth of intraductal MCF10DCIS.com xenografts was similarly impaired along with the frequency of comedo necrosis and stromal activation. In no setting did PCSK5M452I exhibit gain-of-function activity, leading us to conclude that it is hypomorphic and thus compensated by the remaining wild-type allele in MCF10DCIS.com.</p><p><strong>Implications: </strong>This work reassures that an exotic PCSK5 mutation is not responsible for the salient characteristics of the MCF10DCIS.com cell line.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"106-118"},"PeriodicalIF":5.8,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12671455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145377925","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}