Pub Date : 2022-05-14DOI: 10.1186/s13058-022-01526-y
B. Rousseau, Sengottuvelan Murugan, Ajay Palagani, D. Sarkar
{"title":"Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling","authors":"B. Rousseau, Sengottuvelan Murugan, Ajay Palagani, D. Sarkar","doi":"10.1186/s13058-022-01526-y","DOIUrl":"https://doi.org/10.1186/s13058-022-01526-y","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80577043","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}
Pub Date : 2022-05-09DOI: 10.1186/s13058-022-01527-x
Jieling Zheng, Bin Zhang
{"title":"Biological interpretation of prognostic radiomic score by correlating with tumor heterogeneity and microenvironment","authors":"Jieling Zheng, Bin Zhang","doi":"10.1186/s13058-022-01527-x","DOIUrl":"https://doi.org/10.1186/s13058-022-01527-x","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772621","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}
Pub Date : 2022-05-03DOI: 10.1186/s13058-022-01525-z
W. Ho, Andrew M. K. Law, Etienne Masle-Farquhar, Lesley E Castillo, A. Mawson, Moira K. O’Bryan, C. Goodnow, D. Gallego-Ortega, S. Oakes, C. Ormandy
{"title":"Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases","authors":"W. Ho, Andrew M. K. Law, Etienne Masle-Farquhar, Lesley E Castillo, A. Mawson, Moira K. O’Bryan, C. Goodnow, D. Gallego-Ortega, S. Oakes, C. Ormandy","doi":"10.1186/s13058-022-01525-z","DOIUrl":"https://doi.org/10.1186/s13058-022-01525-z","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44167151","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}
Pub Date : 2022-04-14DOI: 10.1186/s13058-022-01522-2
Rachel L. Mintz, Mei Wang, Shuaili Xu, G. Colditz, C. Markovic, Adetunji T. Toriola
{"title":"Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women","authors":"Rachel L. Mintz, Mei Wang, Shuaili Xu, G. Colditz, C. Markovic, Adetunji T. Toriola","doi":"10.1186/s13058-022-01522-2","DOIUrl":"https://doi.org/10.1186/s13058-022-01522-2","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80366287","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}
Pub Date : 2022-04-08DOI: 10.1186/s13058-022-01520-4
Zexuan Liu, Junhao Liu, Behnam Ebrahimi, Uday P Pratap, Yi He, Kristin A Altwegg, Weiwei Tang, Xiaonan Li, Zhao Lai, Yidong Chen, Liangfang Shen, Gangadhara R Sareddy, Suryavathi Viswanadhapalli, Rajeshwar R Tekmal, Manjeet K Rao, Ratna K Vadlamudi
Background: Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance.
Methods: We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER+)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER+ BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression.
Results: RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER+ BC patients.
Conclusions: This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.
背景：甲基转移酶SETDB1在乳腺癌（BC）中高表达，然而，SETDB1促进BC进展为内分泌治疗耐药的机制仍不明确。本研究探讨了SETDB1导致乳腺癌内分泌治疗耐药的机制：我们利用治疗敏感型（MCF7和ZR75）、治疗耐药型（MCF7-TamR、MCF7-FR、MCF7-PELP1cyto、MCF7-SETDB1）雌激素受体α阳性（ER+）BC模型，进行体外细胞活力、集落形成、三维细胞生长试验，研究SETDB1在内分泌耐药中的作用。对亲代细胞和被SETDB1敲除的ER+ BC细胞进行了RNA-seq分析，以确定独特的通路。通过酵母-2杂交筛选确定了SETDB1与PELP1的相互作用，并通过免疫沉淀和GST-拉低试验进行了确认。利用 Western 印迹、报告基因检测、RT-qPCR 和体外甲基化检测进行了机制研究。异种移植实验用于确定 PELP1 在 SETDB1 介导的 BC 进展中的作用：结果：RNA-seq分析表明，SETDB1调节雌激素受体（ER）和Akt靶基因子集的表达，而这些基因会导致内分泌治疗耐药。重要的是，通过酵母-两系杂交筛选，我们发现ER核心调节因子PELP1是与SETDB1相互作用的新蛋白。生化分析证实了 SETDB1 和 PELP1 在多种 BC 细胞中的相互作用。机制研究证实，PELP1 是 SETDB1 介导的 Akt 甲基化和磷酸化的必要条件。此外，SETDB1的过表达促进了BC细胞对他莫昔芬的耐药性，而PELP1的敲除则消除了这些影响。我们利用异种移植模型提供了遗传学证据，证明PELP1对SETDB1介导的BC体内进展至关重要。对TCGA数据集的分析表明，在ER+ BC患者中，SETDB1的表达与PELP1的表达呈正相关：本研究表明，PELP1/SETDB1 轴在异常 Akt 激活中起着重要作用，是治疗乳腺癌内分泌治疗耐药的新靶点。
{"title":"SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance.","authors":"Zexuan Liu, Junhao Liu, Behnam Ebrahimi, Uday P Pratap, Yi He, Kristin A Altwegg, Weiwei Tang, Xiaonan Li, Zhao Lai, Yidong Chen, Liangfang Shen, Gangadhara R Sareddy, Suryavathi Viswanadhapalli, Rajeshwar R Tekmal, Manjeet K Rao, Ratna K Vadlamudi","doi":"10.1186/s13058-022-01520-4","DOIUrl":"10.1186/s13058-022-01520-4","url":null,"abstract":"<p><strong>Background: </strong>Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance.</p><p><strong>Methods: </strong>We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER<sup>+</sup>)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER<sup>+</sup> BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression.</p><p><strong>Results: </strong>RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER<sup>+</sup> BC patients.</p><p><strong>Conclusions: </strong>This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.</p>","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83743011","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}
Pub Date : 2022-04-05DOI: 10.1186/s13058-022-01514-2
S. L. Foo, K. Sachaphibulkij, Corinne Lee, Gracemary L. R. Yap, Jianzhou Cui, T. Arumugam, L. Lim
{"title":"Breast cancer metastasis to brain results in recruitment and activation of microglia through annexin-A1/formyl peptide receptor signaling","authors":"S. L. Foo, K. Sachaphibulkij, Corinne Lee, Gracemary L. R. Yap, Jianzhou Cui, T. Arumugam, L. Lim","doi":"10.1186/s13058-022-01514-2","DOIUrl":"https://doi.org/10.1186/s13058-022-01514-2","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772573","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}
Pub Date : 2022-04-01DOI: 10.1186/s13058-022-01518-y
Anne-Laure Renault, J. Dowty, Jason A. Steen, Shuai Li, I. Winship, G. Giles, J. Hopper, M. Southey, T. Nguyen-Dumont
{"title":"Population-based estimates of age-specific cumulative risk of breast cancer for pathogenic variants in ATM","authors":"Anne-Laure Renault, J. Dowty, Jason A. Steen, Shuai Li, I. Winship, G. Giles, J. Hopper, M. Southey, T. Nguyen-Dumont","doi":"10.1186/s13058-022-01518-y","DOIUrl":"https://doi.org/10.1186/s13058-022-01518-y","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772614","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}
Pub Date : 2022-04-01DOI: 10.1186/s13058-022-01521-3
Guus J. J. E. Heynen, Kamil Lisek, Regina Vogel, A. Wulf‐Goldenberg, Joshua Alcaniz, Elodie Montaudon, E. Marangoni, W. Birchmeier
{"title":"Targeting SHP2 phosphatase in breast cancer overcomes RTK-mediated resistance to PI3K inhibitors","authors":"Guus J. J. E. Heynen, Kamil Lisek, Regina Vogel, A. Wulf‐Goldenberg, Joshua Alcaniz, Elodie Montaudon, E. Marangoni, W. Birchmeier","doi":"10.1186/s13058-022-01521-3","DOIUrl":"https://doi.org/10.1186/s13058-022-01521-3","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87336096","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}
Pub Date : 2022-03-21DOI: 10.1186/s13058-022-01519-x
H. Won, J. Ahn, Y. Kim, Jin Sung Kim, J. Song, Hong-Kyu Kim, Jeeyeon Lee, H. Park, Yong-Seok Kim
{"title":"Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society","authors":"H. Won, J. Ahn, Y. Kim, Jin Sung Kim, J. Song, Hong-Kyu Kim, Jeeyeon Lee, H. Park, Yong-Seok Kim","doi":"10.1186/s13058-022-01519-x","DOIUrl":"https://doi.org/10.1186/s13058-022-01519-x","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88005552","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":"Radiomics predicts the prognosis of patients with locally advanced breast cancer by reflecting the heterogeneity of tumor cells and the tumor microenvironment","authors":"Xuanyi Wang, Tiansong Xie, Ju-rui Luo, Zhengrong Zhou, Xiaoli Yu, Xiaomao Guo","doi":"10.1186/s13058-022-01516-0","DOIUrl":"https://doi.org/10.1186/s13058-022-01516-0","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78756858","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}
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