Carcinogenesis最新文献

{"title":"An exploratory genetic model study of osteopontin in rhabdomyosarcoma subtypes.","authors":"Victoria J Allanson, Katherine R Gregory, Wonsik Son, Jinah Kim, Kyle T Hanson, Sonja D Chen, Kavya Kannan, Melvin Lathara, Ganapati Srinivasa, Noah E Berlow, Qianqian Liu, Joel E Michalek, Sergei P Boudko, Charles Keller","doi":"10.1093/carcin/bgag067","DOIUrl":"10.1093/carcin/bgag067","url":null,"abstract":"<p><p>Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children, with distinct biological subtypes. We found that the protein Osteopontin (Ostp) is highly expressed in our genetically engineered mouse models (GEMM) of RMS alveolar and embryonal subtypes. Through GEMM studies and allograft mouse studies, we explored how Ostp expression affects the onset and growth of tumors in vivo. Ostp loss in alveolar RMS tumors and the tumor microenvironment of genetically engineered mice changed the character of the tumors (decreasing multiplicity, decreasing limb predominance, and decreasing tumor stage) without changing tumor-free survival or histological appearance. Similarly, tumor growth rates and metastasis were not different for Ostp-expressing and Ostp-null tumors in orthotopic allograft studies. Conversely, loss of Ostp expression increased tumor incidence in embryonal RMS GEMMs animals compared to mice on an Ostp wild-type background, although the sample size was small. When combined with the clinical correlation of human Osteopontin gene expression and altered patient survival, Ostp in embryonal RMS may be a topic of further interest and investigation.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-processed foods and breast cancer: epidemiology, mechanisms, and prognostic implications.","authors":"Xiaying Kuang, Zhongyao Li, Fang Fang Zhang, Andrea Romanos-Nanclares, A Heather Eliassen","doi":"10.1093/carcin/bgag062","DOIUrl":"10.1093/carcin/bgag062","url":null,"abstract":"<p><p>Ultra-processed foods (UPFs) have become a dominant component of modern diets and are increasingly implicated in metabolic disorders, inflammation, and cancer risk. Emerging epidemiologic evidence suggests that high UPF intake is associated with increased breast cancer incidence and may influence prognosis and survivorship outcomes, although heterogeneity remains across populations and tumor subtypes, and specific UPF exposures. Given the rising incidence of early-onset breast cancer, which coincides with increasing UPF consumption and prolonged early-life exposure, understanding the potential role of UPF exposure in younger populations represents an emerging public health priority. This review synthesizes current findings on UPF consumption, specific UPF subgroups, food additives, and related exposures in relation to breast cancer risk, including early-onset and other subgroup-specific associations, life-course exposure, mechanistic pathways, and prognostic implications. We highlight evidence linking UPFs to metabolic dysregulation, endocrine disruption, microbiome perturbation, oxidative stress, and carcinogen exposure, and discuss the relevance of metabolomics, lipidomics, and other multi-omics approaches in elucidating causal pathways. Finally, we outline research priorities aimed at refining exposure assessment, strengthening causal inference, and informing cancer prevention and survivorship strategies.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why the current evidence does not support classifying e-cigarettes as likely carcinogenic to humans.","authors":"Christopher Junker","doi":"10.1093/carcin/bgag059","DOIUrl":"10.1093/carcin/bgag059","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fueling early tumorigenesis: interplay between the exposome, obesity-driven metabolic dysfunction and early-onset colorectal and breast cancer.","authors":"Mansi Upadhyay, Arianna V Bastian, Thomas D Cardaci, Minjeong Kim, Liza Makowski, Susan E Steck, E Angela Murphy","doi":"10.1093/carcin/bgag063","DOIUrl":"10.1093/carcin/bgag063","url":null,"abstract":"<p><p>Early-onset cancers (EOCs), defined as cancers diagnosed before the age of 50, are increasing globally. This rise cannot be fully explained by improved detection, suggesting the involvement of evolving environmental and lifestyle-related risk factors. In parallel, the global prevalence of obesity has increased substantially, particularly among younger populations. Obesity is increasingly recognized not simply as excess adiposity, but as a systemic metabolic state characterized by insulin resistance, hyperinsulinemia, chronic low-grade inflammation, altered lipid metabolism, hormonal dysregulation, microbiome disruption, and epigenetic remodeling. These perturbations create a pro-tumorigenic environment that may promote early tumor initiation and progression. Importantly, when metabolic dysfunction arises during critical developmental windows, including in utero, childhood, adolescence, and early adulthood, it may establish long-lasting biological programs that influence growth signaling, immune function, and tissue homeostasis. In this context, increasing attention has shifted toward the \"exposome,\" defined as the totality of environmental exposures encountered across the lifespan and their interactions with biological susceptibility. These exposures may contribute to obesity-associated metabolic dysfunction and interact with one another to influence cancer risk, underscoring the multifactorial nature of EOC development. In this review, we integrate epidemiologic and mechanistic evidence linking obesity and metabolic dysfunction to EOCs, with a focus on colorectal and breast cancers. We highlight key biological pathways, including metabolic signaling, inflammation, microbiome alterations, endocrine disruption, and epigenetic reprogramming, and discuss emerging strategies for prevention and early risk stratification. Understanding the interplay between metabolic health and the exposome may provide critical insights into the prevention of EOCs in younger populations.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR87 promotes DMBA/TPA-induced skin tumorigenesis through the YAP-SOX2 axis.","authors":"Biao Guo, Yiyi Liang, Xiaofeng Qin, Zile Yang, Jiahui Yu, Ruoyun Liu, Yijing Ma, Qidan Zheng, Xiyun Ye, Yongyan Dang","doi":"10.1093/carcin/bgag065","DOIUrl":"10.1093/carcin/bgag065","url":null,"abstract":"<p><p>G protein-coupled receptor 87 (GPR87) has been implicated in the growth and progression of several malignancies, but its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, we found that GPR87 was aberrantly upregulated in murine and human skin tumors and in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated HaCaT keratinocytes. Using a 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced mouse skin tumor model, we demonstrated that GPR87 knockout significantly delayed epidermal hyperplasia, tumor initiation, and malignant progression. Consistently, GPR87 knockdown suppresses TPA-induced keratinocyte proliferation, migration, stemness, and epithelial-mesenchymal transition in keratinocytes and cSCC cells. Mechanistically, GPR87 deficiency markedly reduced SOX2 expression in cultured cells and skin lesions. GPR87 knockdown also enhanced mammalian STE20-like serine/threonine kinases 1/2 (MST1/2) and large tumor suppressor kinases (LATS1/2) phosphorylation, increased inhibitory YAP phosphorylation, and suppressed Yes-associated protein (YAP) nuclear localization and downstream transcriptional activity. Importantly, activation of YAP by either YAP(S127A) expression or XMU-MP-1 treatment restored SOX2 expression in GPR87-depleted cells, whereas verteporfin-mediated inhibition of YAP-TEA domain transcription factor (TEAD) activity attenuated TPA-induced SOX2 upregulation. Together, these findings identify GPR87 as a key positive regulator of skin tumor initiation and progression and demonstrate that its tumor-promoting effects are mediated, at least in part, through the YAP-SOX2 axis. GPR87 may therefore represent a potential therapeutic target for cSCC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Childhood, adolescent, and early adult exposures and cancer risk in middle to late adulthood.","authors":"Edward Giovannucci","doi":"10.1093/carcin/bgag055","DOIUrl":"https://doi.org/10.1093/carcin/bgag055","url":null,"abstract":"<p><p>Although most common cancers occur in adulthood, evidence supports that the etiological relevant time period for many cancers can often extend into childhood and adolescence. This fact is especially noteworthy given the recent rise in early-onset cancers, generally defined as cancers before age 50. Two factors could contribute to strong early life influences on cancer. First, an organ may have a specific susceptibility to irreversible genetic damage from exposure at an early life stage. Second, cells with genetic damage established earlier in life will have sufficient time available to transform into cancer because many cancers require multiple decades to fully develop after initiation, and cancers from cell initiated later in life may be averted by competing causes of death. This paper reviews the main types of evidence supporting that both reasons why early-life exposures are likely to be important. First, a brief summary of the multistage process of cancer is provided, followed by insights from the initiation-promotion model of cancer, and then evidence that some tissues may be especially prone to carcinogenic damage at early ages. The review then ends with some emerging data supporting that lifestyle exposures act primarily during adolescence for breast cancer (especially premenopausal/early onset breast cancer) because of greater carcinogenic susceptibility of breast tissue during this time period; in contrast, for colorectal cancer, lifestyle factors are operative throughout life, but early life is particularly important because early tissue damage allows longer time for cancers (especially early-onset colorectal cancer) to have sufficient time to develop.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-processed foods, cancer, and early-onset cancer: a comprehensive review.","authors":"Yin Zhang, Edward L Giovannucci","doi":"10.1093/carcin/bgag068","DOIUrl":"10.1093/carcin/bgag068","url":null,"abstract":"<p><p>The classification of foods according to their degree of processing, and particularly the concept of ultra-processed foods (UPFs), is relatively new. Consumption of UPFs has increased markedly worldwide in recent decades. Their growing consumption has coincided with a rising global burden of cancer, including marked increases in several cancers diagnosed before age 50 years. In this comprehensive review, we summarize trends in ultra-processed food consumption and the sociodemographic, psychological, and behavioral characteristics associated with higher intake. We further review the epidemiological evidence linking UPFs with cancer incidence and mortality, with particular attention to the limited but emerging evidence relevant to early-onset cancer. Potential mechanisms linking UPFs to cancer include unfavorable nutrient displacement, changes in body composition and fat deposition, and increased exposure to additives, processing byproducts, and other chemicals. These influences may converge on a range of biological pathways, including metabolic dysfunction, chronic inflammation, immune dysregulation, gut microbiome disruption, DNA damage and genomic instability, and epigenetic alterations. Substantial uncertainties remain, including heterogeneous exposure definitions and classification practices, limitations in dietary assessment and temporal exposure capture, residual confounding, and the complexity of putative biological mechanisms. We conclude by highlighting key research challenges and future directions, along with considerations related to policy, regulation, and industry practices.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEK/ERK/RSK2 positive feedback loop modulates EMT to promote migration and invasion of triple-negative breast cancer through regulating GALNT5 mRNA stability.","authors":"Shuhui You, Chen Li, Wenbing Sun, Xiaoxiao Wang, Lvqing Huang, Liangzhi Li, Weiqiang Guo, Min Xiang, Li Zhou","doi":"10.1093/carcin/bgag038","DOIUrl":"10.1093/carcin/bgag038","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, which is difficult to diagnose and treat due to lack of biomarkers, high metastasis, and recurrence. Ribosomal protein S6 kinase (RSK2) is frequently overexpressed and hyperactivated, thereby regulating proliferation and metastasis in many solid cancers, including breast cancer. However, the underlying mechanisms of RSK2 in TNBC metastasis are poorly understood. Here, we explored the role of RSK2 in the migration and invasion of TNBC. Our findings revealed that overexpression of RSK2 promoted Epithelial-mesenchymal transition (EMT) to induce migration and invasion of TNBC cells MDA-MB-231 and 4T1, whereas RSK2 knockdown decreased them. Mechanically, our results showed that RSK2 positively regulated the MEK/ERK pathway and enhanced GALNT5 mRNA expression and stability by RNA-seq analysis and experimental validation. Furthermore, knockdown of GALNT5 attenuated the MEK/ERK pathway. Finally, the in vivo results found that RSK2 promoted growth and EMT of TNBC. Collectively, our findings indicated that the MEK/ERK/RSK2 positive feedback loop promoted EMT to induce migration and invasion of TNBC via enhancing GALNT5 mRNA stability, and it was suggested that RSK2 may provide a novel therapeutic target for TNBC patients.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neddylation pathway promotes the ubiquitinated degradation of FBXO21 in lung cancer cells.","authors":"Ying Zhang, Meng Li, Tiangeng Dong, Yunyang Zhou, Wenjuan Zhang, Gaili Chang, Mingsong Wang, Lijun Jia, Lihui Li","doi":"10.1093/carcin/bgag039","DOIUrl":"https://doi.org/10.1093/carcin/bgag039","url":null,"abstract":"<p><p>SCF (Skp1-Cullin1-Fbox protein) is a multi-subunit RING-type E3 ligase and plays critical roles in various pivotal physiological and pathological processes by mediating the ubiquitination and degradation of key proteins. F-box proteins directly bind substrates, thereby determining their specificity, stability, and function. However, the regulatory mechanisms of FBXO21 degradation in human cancers remain largely elusive. In this study, we demonstrated that Neddylation-ROC1 E3 ligase regulates the protein level of FBXO21. Mechanistic studies revealed that Neddylation-ROC1 targeted FBXO21 for ubiquitination and degradation. Moreover, we found that FBXO21 depletion increased p53 protein stability by delaying its degradation, followed by increasing the transcriptional level of p21. Taken together, our findings reveal a previously unrecognized mechanism by which FBXO21 is regulated by Neddylation modification and regulates the p53-p21 signaling pathway.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of the AR-V7 variant and its association with clinicopathologic characteristics in non-prostatic cancers-a systematic review.","authors":"Zaineh Alnoubani, Youssuf Khanafer, Adnan Fojnica, Emir Begagic, Inga Rose, Zoran Gatalica, Semir Vranic","doi":"10.1093/carcin/bgag052","DOIUrl":"10.1093/carcin/bgag052","url":null,"abstract":"<p><p>Androgen receptor splice variant 7 (AR-V7) is associated with resistance to androgen receptor-targeting therapies in prostate cancer, but its prevalence and clinical relevance in non-prostatic cancers remain incompletely characterized. A systematic review was conducted in accordance with PRISMA guidelines. Thirty-four studies, including 4855 clinical cases and 60 cell lines, were included. Overall, AR-V7 positivity was reported in 948/4855 clinical cases (19.5%); however, this represents a descriptive estimate across heterogeneous tumor types, study designs, and detection methods. Breast cancer accounted for 4057 of 4855 clinical cases (83.6%) and 815 of 948 AR-V7-positive cases (86.0%), with a within-cancer prevalence of 20.1%. However, after excluding the TCGA cohort in which AR-V7 was inferred through splice-junction analysis, the prevalence of AR-V7-positive breast cancer decreased to 9%. Higher tumor-specific proportions were observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non-muscle-invasive bladder cancer (82.6%), but these estimates were based on smaller cohorts and should be interpreted cautiously. AR-V7 was present in several treatment-naive non-prostatic cancers, suggesting that it may represent a preexisting molecular feature in selected contexts. Current evidence suggests that AR-V7 warrants further investigation as a candidate biomarker. Standardized detection methods and prospective studies are needed before its clinical utility can be established.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}