Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3180
Yuankun Zhang, Qingxiao Song, Michael Lee, Haidong Tang, Kaniel Cassady, yang-xin fu, Dustin E. Schones, A. Riggs, Ru Feng, D. Zeng
{"title":"Abstract 3180: Blockade of PD-L1 interaction with CD80in transaugments anti-tumor immunity by increasing NOS2 in tumor-associated macrophages","authors":"Yuankun Zhang, Qingxiao Song, Michael Lee, Haidong Tang, Kaniel Cassady, yang-xin fu, Dustin E. Schones, A. Riggs, Ru Feng, D. Zeng","doi":"10.1158/1538-7445.AM2021-3180","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3180","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43146583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3039
R. Lock, K. Evans, Narimanne El-Zein, E. Earley, S. Erickson, B. Teicher, Malcolm A. Smith
Introduction: While children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains poor. Spleen Tyrosine Kinase (SYK), a cytosolic nonreceptor tyrosine kinase, is primarily expressed in the hematopoietic lineage and is essential for B-cell receptor signaling. It is associated with malignant transformation, cancer cell proliferation, and is a prominent tyrosine-phosphorylated protein in B-lineage pediatric ALL (Dolai et al, Cancer Res 76:2766-77, 2016). Fms Related Receptor Tyrosine Kinase 3 (FLT3) is a Class III receptor tyrosine kinase that regulates hematopoiesis. While uncommon in ALL, activating FLT3 mutations and internal tandem duplications are associated with poor outcome. TAK-659 is a dual SYK/FLT3 reversible inhibitor currently undergoing clinical trials against B-cell lymphoma, acute myeloid leukemia and solid tumors. Therefore, it was of interest for the Pediatric Preclinical Testing Consortium to test TAK-659 in vivo against its patient-derived xenograft (PDX) models of pediatric ALL. Methods: SYK and FLT3 mRNA expression in ALL PDXs was quantified by RNAseq (https://pedcbioportal.org) and 8 B-lineage pediatric ALL PDXs (3 B-cell precursor, BCP; 4 mixed-lineage leukemia-rearranged, MLLr; one Philadelphia Chromosome-like, Ph-like) were selected for testing. Engraftment was evaluated by enumerating the proportion of human CD45+ cells (%huCD45+) in the peripheral (PB) blood at weekly intervals. TAK-659 was tested at 60 mg/kg by oral gavage daily for 21 days. Events were defined as %huCD45+ ≥ 25%. At Day 28 post-treatment initiation or event (whichever occurred first), 4 mice/group were humanely killed to assess leukemia infiltration in the spleen and bone marrow (BM). Drug efficacy was assessed by event-free survival (EFS) of treated (T) and control (C) groups by T-C, T/C and stringent objective response measures (Houghton et al, Pediatr Blood Cancer 49:928-40, 2007). Results: The in vivo efficacy of TAK-659 was evaluated against B-lineage PDXs as FLT3 and SYK mRNA expression was higher in the PDXs from this lineage compared with PDXs from T-ALL. TAK-659 was well tolerated and significantly prolonged the time to event in 6/8 PDXs (T-C 0-25.5 days, T/C 1.0-2.2). Only one MLLr-ALL obtained an objective response (partial response) with all other models exhibiting progressive disease. The minimum mean %huCD45+ was significantly reduced in 5/8 PDXs in TAK-659 treated mice compared to control. Despite significant reductions in %huCD45+ in the PB for 5/8 PDXs, TAK-659 did not significantly reduce the spleen or BM infiltration of any PDXs. Conclusion: TAK-659 exhibited low to moderate single-agent in vivo activity against pediatric B-ALL PDXs representative of diverse disease subtypes. (Supported by NCI Grants CA199000 and CA199922) Citation Format: Richard B. Lock, Kathryn Evans, Narimanne El-Zein, Eric J. Earley, Stephen W. Erickson, Beverly A. Tei
虽然儿童急性淋巴细胞白血病(ALL)的治愈率接近90%，但某些高危儿童ALL亚型的预后仍然很差。脾酪氨酸激酶(SYK)是一种细胞质非受体酪氨酸激酶，主要在造血谱系中表达，对b细胞受体信号传导至关重要。它与恶性转化、癌细胞增殖有关，是b系儿童ALL中一个重要的酪氨酸磷酸化蛋白(Dolai等，cancer Res 76:2766-77, 2016)。Fms相关受体酪氨酸激酶3 (FLT3)是一种调节造血功能的III类受体酪氨酸激酶。虽然在ALL中不常见，但激活FLT3突变和内部串联重复与不良预后相关。TAK-659是一种双SYK/FLT3可逆抑制剂，目前正在进行治疗b细胞淋巴瘤、急性髓性白血病和实体瘤的临床试验。因此，儿科临床前试验联盟有兴趣在体内测试TAK-659对其患者来源的异种移植(PDX)儿童ALL模型的疗效。方法:通过RNAseq (https://pedcbioportal.org)和8个b系儿童ALL PDXs(3个b细胞前体，BCP;4混合谱系白血病-重排;选择一个费城染色体样(Ph-like)进行检测。通过每周计数外周血中人CD45+细胞的比例(%huCD45+)来评估移植情况。TAK-659以60 mg/kg的剂量，每天灌胃21天。事件定义为%huCD45+≥25%。在治疗开始或事件发生后第28天(以先发生者为准)，每组4只小鼠被人杀，以评估白血病在脾脏和骨髓的浸润(BM)。通过T-C、T/C和严格的客观反应指标，以治疗组(T)和对照组(C)的无事件生存期(EFS)来评估药物疗效(Houghton等，儿科血癌49:928-40,2007)。结果:TAK-659对b系pdx的体内疗效进行了评估，该谱系的pdx中FLT3和SYK mRNA的表达高于T-ALL的pdx。TAK-659耐受性良好，可显著延长6/8例患者的事件发生时间(T-C 0-25.5天，T/C 1.0-2.2)。只有一种MLLr-ALL获得了客观反应(部分反应)，所有其他模型均表现出疾病的进行性。与对照组相比，TAK-659处理小鼠中5/8 pdx的最小平均%huCD45+显著降低。尽管5/8个pdx的PB中%huCD45+显著降低，但TAK-659没有显著减少任何pdx的脾脏或BM浸润。结论:TAK-659对代表不同疾病亚型的儿童B-ALL pdx具有低至中等的单药体内活性。(由NCI基金CA199000和CA199922资助)引文格式:Richard B. Lock, Kathryn Evans, Narimanne El-Zein, Eric J. Earley, Stephen W. Erickson, Beverly A. Teicher, Malcolm A. SmithSYK/FLT3双抑制剂TAK-659在小儿急性淋巴细胞白血病异种移植模型中的临床前试验联合评估[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要nr 3039。
{"title":"Abstract 3039: Pediatric preclinical testing consortium evaluation of the dual SYK/FLT3 inhibitor TAK-659 in xenograft models of pediatric acute lymphoblastic leukemia","authors":"R. Lock, K. Evans, Narimanne El-Zein, E. Earley, S. Erickson, B. Teicher, Malcolm A. Smith","doi":"10.1158/1538-7445.AM2021-3039","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3039","url":null,"abstract":"Introduction: While children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains poor. Spleen Tyrosine Kinase (SYK), a cytosolic nonreceptor tyrosine kinase, is primarily expressed in the hematopoietic lineage and is essential for B-cell receptor signaling. It is associated with malignant transformation, cancer cell proliferation, and is a prominent tyrosine-phosphorylated protein in B-lineage pediatric ALL (Dolai et al, Cancer Res 76:2766-77, 2016). Fms Related Receptor Tyrosine Kinase 3 (FLT3) is a Class III receptor tyrosine kinase that regulates hematopoiesis. While uncommon in ALL, activating FLT3 mutations and internal tandem duplications are associated with poor outcome. TAK-659 is a dual SYK/FLT3 reversible inhibitor currently undergoing clinical trials against B-cell lymphoma, acute myeloid leukemia and solid tumors. Therefore, it was of interest for the Pediatric Preclinical Testing Consortium to test TAK-659 in vivo against its patient-derived xenograft (PDX) models of pediatric ALL. Methods: SYK and FLT3 mRNA expression in ALL PDXs was quantified by RNAseq (https://pedcbioportal.org) and 8 B-lineage pediatric ALL PDXs (3 B-cell precursor, BCP; 4 mixed-lineage leukemia-rearranged, MLLr; one Philadelphia Chromosome-like, Ph-like) were selected for testing. Engraftment was evaluated by enumerating the proportion of human CD45+ cells (%huCD45+) in the peripheral (PB) blood at weekly intervals. TAK-659 was tested at 60 mg/kg by oral gavage daily for 21 days. Events were defined as %huCD45+ ≥ 25%. At Day 28 post-treatment initiation or event (whichever occurred first), 4 mice/group were humanely killed to assess leukemia infiltration in the spleen and bone marrow (BM). Drug efficacy was assessed by event-free survival (EFS) of treated (T) and control (C) groups by T-C, T/C and stringent objective response measures (Houghton et al, Pediatr Blood Cancer 49:928-40, 2007). Results: The in vivo efficacy of TAK-659 was evaluated against B-lineage PDXs as FLT3 and SYK mRNA expression was higher in the PDXs from this lineage compared with PDXs from T-ALL. TAK-659 was well tolerated and significantly prolonged the time to event in 6/8 PDXs (T-C 0-25.5 days, T/C 1.0-2.2). Only one MLLr-ALL obtained an objective response (partial response) with all other models exhibiting progressive disease. The minimum mean %huCD45+ was significantly reduced in 5/8 PDXs in TAK-659 treated mice compared to control. Despite significant reductions in %huCD45+ in the PB for 5/8 PDXs, TAK-659 did not significantly reduce the spleen or BM infiltration of any PDXs. Conclusion: TAK-659 exhibited low to moderate single-agent in vivo activity against pediatric B-ALL PDXs representative of diverse disease subtypes. (Supported by NCI Grants CA199000 and CA199922) Citation Format: Richard B. Lock, Kathryn Evans, Narimanne El-Zein, Eric J. Earley, Stephen W. Erickson, Beverly A. Tei","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43207883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3149
Beilei Liu
{"title":"Abstract 3149: Investigation of the potential therapeutic value of CAF-derived milk fat globule-EGF factor 8 protein (MFG-E8) in esophageal squamous cell carcinoma","authors":"Beilei Liu","doi":"10.1158/1538-7445.AM2021-3149","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3149","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41989657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3147
F. Barthel, N. Verburg, R. Rockne, R. Eijgelaar, K. Anderson, D. J. Müller, S. Branciamore, K. Johnson, P. Wesseling, P. D. W. Hamer, R. Verhaak
{"title":"Abstract 3147: Stereotactic image-guided epigenome profiling reveals a neural stem cell evolutionary origin of diffuse gliomas","authors":"F. Barthel, N. Verburg, R. Rockne, R. Eijgelaar, K. Anderson, D. J. Müller, S. Branciamore, K. Johnson, P. Wesseling, P. D. W. Hamer, R. Verhaak","doi":"10.1158/1538-7445.AM2021-3147","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3147","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42241280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2891
N. Li, Shile Huang
Metastasis has been considered as one of the cancer hallmarks. Approximately 90% of cancer-related death is due to cancer metastasis. Tumor cell migration is a prerequisite for cancer metastasis. Protein phosphatase 5 (PP5) is a serine/threonine protein phosphatase that belongs to the phosphoprotein phosphatase (PPP) family including PP1 and PP2A. It is well known that PP5 regulates apoptosis, proliferation, and stress response. However, the role of PP5 in the regulation of cell motility is only beginning to be recognized, and the mechanism of PP5 regulation of cell motility is largely unknown. In this study, our tissue microarray (TMA) studies showed the expression of PP5 increased with the stages of prostate cancer, which is consistent with the previous findings that there is a positive correlation between PP5 overexpression and breast cancer metastases. Furthermore, by the single-cell motility assay, we found that overexpression of PP5 increased the motility of various tumor cells, whereas knockdown of PP5 decreased the cell motility, suggesting that PP5 positively regulates cell motility. As focal adhesion kinase (FAK) is a key regulator of cell motility, and a report has shown that PP5 forms a complex with ASK1, FAK, CXCR4 in wounded alveolar epithelial cancer cells, we examined whether PP5 activates FAK. The Western blotting results showed that overexpression of PP5 did not obviously affect the phosphorylation of FAK. The results suggest that PP5 regulates cell motility through a new mechanism. Further research is on the way to identify how PP5 positively regulates cell motility. (Supported by the Feist-Weiller Cancer Center, LSU Health Sciences Center, Shreveport, LA, USA.) Citation Format: n Li, Shile Huang. Protein phosphatase 5 regulation of cell motility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2891.
{"title":"Abstract 2891: Protein phosphatase 5 regulation of cell motility","authors":"N. Li, Shile Huang","doi":"10.1158/1538-7445.AM2021-2891","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2891","url":null,"abstract":"Metastasis has been considered as one of the cancer hallmarks. Approximately 90% of cancer-related death is due to cancer metastasis. Tumor cell migration is a prerequisite for cancer metastasis. Protein phosphatase 5 (PP5) is a serine/threonine protein phosphatase that belongs to the phosphoprotein phosphatase (PPP) family including PP1 and PP2A. It is well known that PP5 regulates apoptosis, proliferation, and stress response. However, the role of PP5 in the regulation of cell motility is only beginning to be recognized, and the mechanism of PP5 regulation of cell motility is largely unknown. In this study, our tissue microarray (TMA) studies showed the expression of PP5 increased with the stages of prostate cancer, which is consistent with the previous findings that there is a positive correlation between PP5 overexpression and breast cancer metastases. Furthermore, by the single-cell motility assay, we found that overexpression of PP5 increased the motility of various tumor cells, whereas knockdown of PP5 decreased the cell motility, suggesting that PP5 positively regulates cell motility. As focal adhesion kinase (FAK) is a key regulator of cell motility, and a report has shown that PP5 forms a complex with ASK1, FAK, CXCR4 in wounded alveolar epithelial cancer cells, we examined whether PP5 activates FAK. The Western blotting results showed that overexpression of PP5 did not obviously affect the phosphorylation of FAK. The results suggest that PP5 regulates cell motility through a new mechanism. Further research is on the way to identify how PP5 positively regulates cell motility. (Supported by the Feist-Weiller Cancer Center, LSU Health Sciences Center, Shreveport, LA, USA.) Citation Format: n Li, Shile Huang. Protein phosphatase 5 regulation of cell motility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2891.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42267807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2709
Fang Liu, Jun Zhou, Tanima Kundu-Roy, Joseph Wahler, J. So, Yong Lin, Y. Lou, N. Barnard, I. Matsuura, N. Suh
{"title":"Abstract 2709: CD44 inhibits DCIS progression to invasive carcinoma","authors":"Fang Liu, Jun Zhou, Tanima Kundu-Roy, Joseph Wahler, J. So, Yong Lin, Y. Lou, N. Barnard, I. Matsuura, N. Suh","doi":"10.1158/1538-7445.AM2021-2709","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2709","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49570385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2727
Vasiliki Stravokefalou, D. Stellas, S. Karaliota, Bethany A. Nagy, T. Guerin, S. Kozlov, B. Felber, G. Pavlakis
{"title":"Abstract 2727: Heterodimeric IL-15 (hetIL-15) affects conventional dendritic cells and a distinct novel dendritic cell population in different mouse cancer models of breast and pancreatic cancer","authors":"Vasiliki Stravokefalou, D. Stellas, S. Karaliota, Bethany A. Nagy, T. Guerin, S. Kozlov, B. Felber, G. Pavlakis","doi":"10.1158/1538-7445.AM2021-2727","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2727","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49611457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-130
Ansam Sinjab, Guangchun Han, Warapen Treekitkarnmongkol, K. Hara, P. Brennan, M. Dang, Dapeng Hao, Ruiping Wang, E. Dai, H. Dejima, Jiexin Zhang, Elena P. Bogatenkova, B. Sánchez-Espiridión, K. Chang, Danielle R. Little, Samer Bazzi, L. Tran, K. Krysan, C. Behrens, D. Duose, E. Parra, M. G. Raso, L. Solis, J. Fukuoka, Jianjun Zhang, B. Sepesi, T. Cascone, L. Byers, D. Gibbons, Jichao Chen, S. Moghaddam, E. Ostrin, D. Rosen, J. Heymach, P. Scheet, S. Dubinett, I. Wistuba, J. Fujimoto, Christopher S Stevenson, A. Spira, Linghua Wang, H. Kadara
{"title":"Abstract 130: Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing","authors":"Ansam Sinjab, Guangchun Han, Warapen Treekitkarnmongkol, K. Hara, P. Brennan, M. Dang, Dapeng Hao, Ruiping Wang, E. Dai, H. Dejima, Jiexin Zhang, Elena P. Bogatenkova, B. Sánchez-Espiridión, K. Chang, Danielle R. Little, Samer Bazzi, L. Tran, K. Krysan, C. Behrens, D. Duose, E. Parra, M. G. Raso, L. Solis, J. Fukuoka, Jianjun Zhang, B. Sepesi, T. Cascone, L. Byers, D. Gibbons, Jichao Chen, S. Moghaddam, E. Ostrin, D. Rosen, J. Heymach, P. Scheet, S. Dubinett, I. Wistuba, J. Fujimoto, Christopher S Stevenson, A. Spira, Linghua Wang, H. Kadara","doi":"10.1158/1538-7445.AM2021-130","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-130","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42330859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2837
M. Sosa, Carolina Rodriguez-Tirado, Nupura Kale, M. Carlini, N. Shrivastava, Bassem D. Khalil, J. Bravo-Cordero, Melissa Alexander, Jiayi Ji
Cancer cells disseminate during very early and sometimes asymptomatic stages of tumor progression. Granted that biological barriers to tumorigenesis exist, there must also be limiting steps to early dissemination, all of which remain largely unknown. We report that the orphan nuclear receptor NR2F1/COUP-TF1 serves as a barrier to early dissemination. High-resolution intravital imaging revealed that loss of function of NR2F1 in HER2+ early cancer cells increased in vivo dissemination without accelerating mammary tumor formation. NR2F1 expression was positively regulated by the tumor suppressive MMK3/6-p38-MAPK pathway and downregulated by HER2 and Wnt4 oncogenic signaling. NR2F1 downregulation by HER2 in early cancer cells led to decreased E-cadherin expression and β-catenin membrane localization, disorganized laminin 5 deposition, and increased expression of CK14, TWIST1, ZEB1 and PRRX1. Our findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 downstream of HER2 signaling. Citation Format: Maria Soledad Sosa, Carolina Rodriguez-Tirado, Nupura Kale, Maria Carlini, Nitisha Shrivastava, Bassem Khalil, Javier Bravo-Cordero, Melissa Alexander, Jiayi Ji. NR2F1 is a barrier to early dissemination of pre-malignant mammary cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2837.
{"title":"Abstract 2837: NR2F1 is a barrier to early dissemination of pre-malignant mammary cells","authors":"M. Sosa, Carolina Rodriguez-Tirado, Nupura Kale, M. Carlini, N. Shrivastava, Bassem D. Khalil, J. Bravo-Cordero, Melissa Alexander, Jiayi Ji","doi":"10.1158/1538-7445.AM2021-2837","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2837","url":null,"abstract":"Cancer cells disseminate during very early and sometimes asymptomatic stages of tumor progression. Granted that biological barriers to tumorigenesis exist, there must also be limiting steps to early dissemination, all of which remain largely unknown. We report that the orphan nuclear receptor NR2F1/COUP-TF1 serves as a barrier to early dissemination. High-resolution intravital imaging revealed that loss of function of NR2F1 in HER2+ early cancer cells increased in vivo dissemination without accelerating mammary tumor formation. NR2F1 expression was positively regulated by the tumor suppressive MMK3/6-p38-MAPK pathway and downregulated by HER2 and Wnt4 oncogenic signaling. NR2F1 downregulation by HER2 in early cancer cells led to decreased E-cadherin expression and β-catenin membrane localization, disorganized laminin 5 deposition, and increased expression of CK14, TWIST1, ZEB1 and PRRX1. Our findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 downstream of HER2 signaling. Citation Format: Maria Soledad Sosa, Carolina Rodriguez-Tirado, Nupura Kale, Maria Carlini, Nitisha Shrivastava, Bassem Khalil, Javier Bravo-Cordero, Melissa Alexander, Jiayi Ji. NR2F1 is a barrier to early dissemination of pre-malignant mammary cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2837.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42565653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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