Role of UHRF1 in osteosarcoma metastasis

项目摘要 这一多样性补充应用程序建立在研究RB基因变化的父母拨款的基础上 转录共抑制因子1(RB1)基因与死亡率、转移和不良相关 骨肉瘤对化疗的反应。我们最近发现了类泛素，含有PHD和RING Finger结构域-1(Uhrf1)，作为一种关键的表观遗传调节因子，在骨肉瘤中上调。我们的预赛 研究表明，uhrf1过表达导致细胞增殖、迁移、侵袭和 转移。在这项补充资料中，我们建议扩大父母津贴的范围，以澄清 骨肉瘤中uhrf1过表达促进肿瘤侵袭和转移的机制 转移。我们建议研究uhrf1在癌细胞和肿瘤相互作用中的作用。 通过外切体改变的微环境。外周小体已被确认为一个重要的因素 癌细胞和间质细胞对转移性表型的诱导。我们假设uhrf1 过度表达有助于改变外切体的形成和/或外切体的运输，这有助于 骨肉瘤的转移。总体而言，这项研究建议将扩大我们对uhrf1作用的理解。 在骨肉瘤转移中。

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.