Cancer research最新文献

{"title":"Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer.","authors":"Michela Menegollo, Robert B Bentham, Tiago Henriques, Seow Q Ng, Ziyu Ren, Clarinde Esculier, Sia Agarwal, Emily T Y Tong, Clement Lo, Sanjana Ilangovan, Zorka Szabadkai, Matteo Suman, Neill Patani, Avinash Ghanate, Kevin Bryson, Robert C Stein, Mariia Yuneva, Gyorgy Szabadkai","doi":"10.1158/0008-5472.CAN-23-3172","DOIUrl":"10.1158/0008-5472.CAN-23-3172","url":null,"abstract":"<p><p>Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labeled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states. Significance: A method for identifying the transcriptomic signatures of metabolic switches underlying divergent routes of cellular transformation stratifies breast cancer into metabolic subtypes, predicting their biology, architecture, and clinical outcome.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dotting Out AML by Targeting Fibrillarin.","authors":"Hanzhi Luo, Michael G Kharas","doi":"10.1158/0008-5472.CAN-24-2125","DOIUrl":"10.1158/0008-5472.CAN-24-2125","url":null,"abstract":"<p><p>Dysregulated biomolecular condensates, formed through multivalent interactions among proteins and nucleic acids, have been recently identified to drive tumorigenesis. In acute myeloid leukemia (AML), condensates driven by RNA-binding proteins alter transcriptional networks. Yang and colleagues performed a CRISPR screen and identified fibrillarin (FBL) as a new driver in AML leukemogenesis. FBL depletion caused cell cycle arrest and death in AML cells, with minimal impact on normal cells. FBL's phase separation domains are essential for pre-rRNA processing, influencing AML cell survival by regulating ribosome biogenesis and the translation of oncogenic proteins like MYC. Therapeutically, the chemotherapeutic agent CGX-635 targets FBL, inducing its aggregation, impairing pre-rRNA processing, and reducing AML cell survival. This highlights FBL's phase separation as a therapeutic vulnerability in AML. These findings suggest that targeting the phase separation properties of RNA-binding proteins could offer a novel and effective strategy for AML treatment. Further research into condensate dynamics in cancer and development of condensate-modulating drugs holds significant promise for future cancer therapies.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ku70 Binding to YAP Alters PARP1 Ubiquitination to Regulate Genome Stability and Tumorigenesis.","authors":"Yinyin Shu, Xiaoni Jin, Mintao Ji, Zhisen Zhang, Xiuxiu Wang, Haisheng Liang, Shuangshuang Lu, Shuai Dong, Yiping Lin, Yuhan Guo, Qiuyu Zhuang, Yuhong Wang, Zhe Lei, Lingchuan Guo, Xuanyu Meng, Guangming Zhou, Wensheng Zhang, Lei Chang","doi":"10.1158/0008-5472.CAN-23-4034","DOIUrl":"10.1158/0008-5472.CAN-23-4034","url":null,"abstract":"<p><p>Yes-associated protein (YAP) is a central player in cancer development, with functions extending beyond its recognized role in cell growth regulation. Recent work has identified a link between YAP/transcriptional coactivator with PDZ-binding motif (TAZ) and the DNA damage response. Here, we investigated the mechanistic underpinnings of the cross-talk between DNA damage repair and YAP activity. Ku70, a key component of the nonhomologous end joining pathway to repair DNA damage, engaged in a dynamic competition with TEAD4 for binding to YAP, limiting the transcriptional activity of YAP. Depletion of Ku70 enhanced interaction between YAP and TEAD4 and boosted YAP transcriptional capacity. Consequently, Ku70 loss enhanced tumorigenesis in colon cancer and hepatocellular carcinoma (HCC) in vivo. YAP impeded DNA damage repair and elevated genome instability by inducing PARP1 degradation through the SMURF2-mediated ubiquitin-proteasome pathway. Analysis of samples from patients with HCC substantiated the link between Ku70 expression, YAP activity, PARP1 levels, and genome instability. In conclusion, this research provides insight into the mechanistic interactions between YAP and key regulators of DNA damage repair, highlighting the role of a Ku70-YAP-PARP1 axis in preserving genome stability. Significance: Increased yes-associated protein transcriptional activity stimulated by loss of Ku70 induces PARP1 degradation by upregulating SMURF2 to inhibit DNA damage, driving genome instability and tumorigenesis.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clocking Cancer Immunotherapy Responses.","authors":"Catherine L Wang, Xue Zhang, Chi V Dang","doi":"10.1158/0008-5472.CAN-24-2083","DOIUrl":"10.1158/0008-5472.CAN-24-2083","url":null,"abstract":"<p><p>Two recent papers document that responses to immunotherapy are circadian and peak at the end of resting phase (evening) of mice with syngeneic and genetic models of cancers. The circadian effect is attributed to diurnal T-cell trafficking through the endothelium on the one hand, and to the circadian expression of PD-L1 on myeloid suppressors on the other. Overall, it appears that tumor immunity as a system, including dendritic cell function, behaves in a circadian manner that is also observed in patients in cancer immunotherapy clinical trials. Importantly, these observations uncover time-of-day as an unforeseen variable for cancer immunotherapy responses. This insight on the immune circadian clock should be further explored to enhance immunotherapy responses in the clinic.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARID1A-Deficient Tumors Acquire Immunogenic Neoantigens during the Development of Resistance to Targeted Therapy.","authors":"Masahiro Okada, Satoru Yamasaki, Hiroshi Nakazato, Yuhya Hirahara, Takuya Ishibashi, Masami Kawamura, Kanako Shimizu, Shin-Ichiro Fujii","doi":"10.1158/0008-5472.CAN-23-2846","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-2846","url":null,"abstract":"<p><p>Neoantigen-based immunotherapy is an attractive potential treatment for previously intractable tumors. To effectively broaden the application of this approach, stringent biomarkers are crucial to identify responsive patients. ARID1A, a frequently mutated subunit of SWI/SNF chromatin remodeling complex, has been reported to determine tumor immunogenicity in some cohorts; however, mutations and deletions of ARID1A are not always linked to clinical responses to immunotherapy. In this study, we investigated immunotherapeutic responses based on ARID1A status in targeted therapy-resistant cancers. Mouse and human BRAFV600E melanomas with or without ARID1A expression were transformed into resistant to vemurafenib, an FDA-approved specific BRAFV600E inhibitor. Anti-PD-1 antibody treatment enhanced antitumor immune responses in vemurafenib-resistant ARID1A-deficient tumors but not in ARID1A-intact tumors or vemurafenib-sensitive ARID1A-deficient tumors. Neoantigens derived from accumulated somatic mutations during vemurafenib resistance were highly expressed in ARID1A-deficient tumors and promoted tumor immunogenicity. Furthermore, the newly generated neoantigens could be utilized as immunotherapeutic targets by vaccines. Finally, targeted therapy resistance-specific neoantigen in experimental human melanoma cells lacking ARID1A were validated to elicit T-cell receptor responses. Collectively, the classification of ARID1A-mutated tumors based on vemurafenib resistance as an additional indicator of immunotherapy response will enable a more accurate prediction to guide cancer treatment. Furthermore, the neoantigens that emerge with therapy resistance can be promising therapeutic targets for refractory tumors. Significance: Chemotherapy resistance promotes the acquisition of immunogenic neoantigens in ARID1A-deficient tumors that confer sensitivity to immune checkpoint blockade and can be utilized for developing antitumor vaccines, providing strategies to improve immunotherapy efficacy.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression.","authors":"Lingling Li, Dongxian Jiang, Hui Liu, Chunmei Guo, Qiao Zhang, Xuedong Li, Xiaojian Chen, Zheqi Chen, Jinwen Feng, Subei Tan, Wen Huang, Jie Huang, Chen Xu, Chen-Ying Liu, Wei Yu, Yingyong Hou, Chen Ding","doi":"10.1158/0008-5472.CAN-23-1878","DOIUrl":"10.1158/0008-5472.CAN-23-1878","url":null,"abstract":"<p><p>Colorectal cancer is the second most common malignant tumor worldwide. Analysis of the changes that occur during colorectal cancer progression could provide insights into the molecular mechanisms driving colorectal cancer development and identify improved treatment strategies. In this study, we performed an integrated multiomic analysis of 435 trace tumor samples from 148 patients with colorectal cancer, covering nontumor, intraepithelial neoplasia (IEN), infiltration, and advanced stage colorectal cancer phases. Proteogenomic analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidative phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, which occurred predominantly in the IEN and infiltration phases, respectively, and impacted the cell cycle. Mutations in TP53 were frequent in the advanced stage colorectal cancer phase and associated with the tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of colorectal cancer based on consensus molecular subtype and colorectal cancer intrinsic subtype classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of colorectal cancer based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided colorectal cancer. The AOM/DSS-induced colorectal cancer carcinogenesis mouse model indicated that DDX5 deletion due to chr17q loss promoted colorectal cancer development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of colorectal cancer and identifying the potential therapeutic targets. Significance: Characterization of the proteogenomic landscape of colorectal cancer during progression provides a multiomic map detailing the alterations in each stage of carcinogenesis and suggesting potential diagnostic and therapeutic approaches for patients.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.","authors":"Geonhui Lee, Claudia Wong, Anna Cho, Junior J West, Ashleigh J Crawford, Gabriella C Russo, Bishwa R Si, Jungwoo Kim, Lauren Hoffner, Cholsoon Jang, Moonjung Jung, Robert D Leone, Konstantinos Konstantopoulos, Andrew J Ewald, Denis Wirtz, Sangmoo Jeong","doi":"10.1158/0008-5472.CAN-23-3082","DOIUrl":"10.1158/0008-5472.CAN-23-3082","url":null,"abstract":"<p><p>The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers. Significance: E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin-expressing tumors.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1.","authors":"Di Liu, Mengqiu Li, Zhiyao Zhao, Liang Zhou, Feng Zhi, Zhiyong Guo, Jun Cui","doi":"10.1158/0008-5472.CAN-23-3971","DOIUrl":"10.1158/0008-5472.CAN-23-3971","url":null,"abstract":"<p><p>Immunotherapy has greatly improved cancer treatment in recent years by harnessing the immune system to target cancer cells. The first immunotherapeutic agent approved by the FDA was IFNα. Treatment with IFNα can lead to effective immune activation and attenuate tumor immune evasion, but persistent treatment has been shown to elicit immunosuppressive effects. Here, we identified an autophagy-dependent mechanism by which IFNα triggers tumor immune evasion by upregulating PD-L1 to suppress the antitumor activity of CD8+ T cells. Mechanistically, IFNα increased the transcription of TRIM14, which recruited the deubiquitinase USP14 to inhibit the autophagic degradation of PD-L1. USP14 removed K63-linked ubiquitin chains from PD-L1, impairing its recognition by the cargo receptor p62 (also known as SQSTM1) for subsequent autophagic degradation. Combining the USP14 inhibitor IU1 with IFNα and anti-CTLA4 treatment effectively suppressed tumor growth without significant toxicity. This work suggests a strategy for targeting selective autophagy to abolish PD-L1-mediated cancer immune evasion. Significance: IFNα-induced TRIM14 transcription suppresses antitumor immunity by recruiting USP14 to inhibit autophagic degradation of PD-L1, indicating that targeting this axis could be an effective immunotherapeutic approach for treating cancer.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma.","authors":"Li Li, Dacheng Xie, Shijun Yu, Muyuan Ma, Kailing Fan, Jingde Chen, Mengxi Xiu, Keping Xie, Yandong Li, Yong Gao","doi":"10.1158/0008-5472.CAN-23-1167","DOIUrl":"10.1158/0008-5472.CAN-23-1167","url":null,"abstract":"<p><p>Cellular oxidative stress plays a key role in the development and progression of hepatocellular carcinoma (HCC). A better understanding of the processes that regulate reactive oxygen species (ROS) homeostasis could uncover improved strategies for treating HCC. Herein, we identified protein kinase with-no-lysine kinase 1 (WNK1) as an antioxidative factor and therapeutic target in HCC. In human HCC, WNK1 expression was increased and correlated with poor patient prognosis. WNK1 knockdown significantly inhibited cell proliferation and xenograft tumor growth. Mechanistically, WNK1 competed with nuclear factor erythroid 2-related factor 2 (NRF2) for binding with the partial Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), reducing NRF2 ubiquitination and promoting NRF2 accumulation and nuclear translocation to increase antioxidant response. WNK1 silencing increased H2O2-induced apoptosis and inhibited cell growth by elevating ROS levels, which could be rescued by treatment with the antioxidant N-acetylcysteine and NRF2 activator tert-butylhydroquinone. Liver-specific WNK1 knockout mouse models of HCC substantiated that WNK1 promoted HCC development by regulating ROS levels. WNK463, an inhibitor of the WNK kinase family, suppressed HCC progression and altered the redox status. These findings suggest that WNK1 plays a critical role in HCC development and progression and that the WNK1-oxidative stress axis may be a promising therapeutic target for HCC. Significance: Inhibiting WNK1 induces NRF2 degradation and reduces the oxidative stress response to suppress hepatocellular carcinoma growth, indicating that targeting the WNK1-KEAP1-NRF2 axis is a potential strategy to treat liver cancer.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.","authors":"Sydney J Conner, Hannah B Borges, Justinne R Guarin, Thomas J Gerton, Anna Yui, Kenneth J Salhany, Diamond N Mensah, Grace A Hamilton, Giang H Le, Katherine C Lew, Crystal Zhang, Madeleine J Oudin","doi":"10.1158/0008-5472.CAN-23-2526","DOIUrl":"10.1158/0008-5472.CAN-23-2526","url":null,"abstract":"<p><p>Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}