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Role of UHRF1 in osteosarcoma metastasis

UHRF1在骨肉瘤转移中的作用

基本信息

批准号：
10310790
负责人：
Claudia Andrea Benavente
金额：
$ 11.11万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10310790
关键词：
Adhesions Cell Line Cell Proliferation Cells Cellular Structures Clinical Data Development Epigenetic Process Exocytosis Genes Genetic Transcription Genetic study Genetically Engineered Mouse Grant Human In Vitro Incidence Knock-out Knockout Mice Malignant Neoplasms Metastatic Neoplasm to the Lung Metastatic Osteosarcoma MicroRNAs Modeling Mutation Neoplasm Metastasis Nonmetastatic PHD Finger Pathway interactions Phenotype Protein Secretion Proteins Research Proposals Ring Finger Domain Role Stromal Cells Survival Rate TP53 gene Testing Tumor Cell Invasion Ubiquitin angiogenesis cancer cell chemotherapy exosome gain of function genetic corepressor in vivo insight loss of function migration mortality mouse model novel therapeutic intervention osteosarcoma overexpression response therapeutic target transcriptomics tumor tumor microenvironment tumorigenesis

项目摘要

Project Summary This Diversity Supplement application builds on a parental grant studying the genetic alterations at the RB transcriptional corepressor 1 (RB1) gene that are associated with increased mortality, metastasis and poor response to chemotherapy in osteosarcoma. We recently identified ubiquitin-like, containing PHD and RING finger domains-1 (UHRF1), as a key epigenetic regulator that is upregulated in osteosarcoma. Our preliminary studies suggest that UHRF1 overexpression results in increased cell proliferation, migration, invasion, and metastasis. For this supplement, we propose to expand the scope of our parental grant to elucidate the mechanisms through which UHRF1 overexpression in osteosarcoma contributes to tumor invasion and metastasis. We propose to examine the role of UHRF1 on the interaction between cancer cells and the tumor microenvironment through exosome alterations. Exosomes have been identified as an important factor in the modulation of cancer and stromal cells towards induction of a metastatic phenotype. We hypothesize that UHRF1 overexpression contributes to altered exosome formation and/or exosomal cargo and this contributes to metastasis in osteosarcoma. Overall, this research proposal will broaden our understanding of the role of UHRF1 in osteosarcoma metastasis.

项目概要该多样性补充申请以父母资助为基础，研究 RB 的基因改变转录辅阻遏物 1 (RB1) 基因与死亡率增加、转移和贫困有关骨肉瘤对化疗的反应。我们最近发现了类泛素，包含 PHD 和 RING Finger 结构域-1 (UHRF1)，作为骨肉瘤中上调的关键表观遗传调节因子。我们的初步研究表明，UHRF1 过度表达会导致细胞增殖、迁移、侵袭和迁移增加转移。对于此补充，我们建议扩大家长补助金的范围，以阐明 UHRF1在骨肉瘤中过度表达导致肿瘤侵袭和侵袭的机制转移。我们建议检查 UHRF1 在癌细胞与肿瘤之间相互作用中的作用通过外泌体改变微环境。外泌体已被确定为重要因素调节癌症和基质细胞以诱导转移表型。我们假设UHRF1 过度表达有助于改变外泌体形成和/或外泌体货物，这有助于骨肉瘤的转移。总的来说，这项研究计划将拓宽我们对 UHRF1 作用的理解在骨肉瘤转移中。