The role of PLK1 in prostate cancer

PLK1在前列腺癌中的作用

基本信息

批准号：
9889905
负责人：
ZHENG FU
金额：
$ 34.88万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9889905
关键词：
Address American Animal Model Apoptosis Applications Grants Attention Biochemical Biological Models Cancer Etiology Cancer Patient Cancer Prognosis Cell Cycle Cell division Cellular Morphology Cessation of life Clinical Cytokinesis Data Development Down-Regulation Epithelial Epithelial Cells Epithelium Event Fibroblasts Genetic Human In Vitro Knowledge Link Malignant Neoplasms Malignant neoplasm of prostate Mesenchymal Metastatic Prostate Cancer Mitosis Mitotic Molecular Mus Neoplasm Metastasis Oncogenic Organ PLK1 gene PTEN gene Phosphotransferases Play Population Preventive Property Prostate Protein-Serine-Threonine Kinases Proto-Oncogenes Regulation Role Series Signal Transduction Testing Therapeutic Transgenes Transgenic Mice Transgenic Model Treatment Protocols Work Xenograft procedure anti-cancer base cancer cell cancer initiation cancer type castration resistant prostate cancer cell motility design epithelial to mesenchymal transition experimental study in vivo men metaplastic cell transformation mouse model novel overexpression prostate cancer cell prostate cancer cell line prostate cancer model prostate carcinogenesis public health relevance standard care treatment optimization tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Mammalian polo-like kinase 1 (PLK1), a major kinase with pivotal roles in multiple aspects of cell division, is closely associated with human cancer development and is frequently overexpressed in various cancers, including prostate cancer (PCa). PLK1 has been postulated to be a proto-oncogene; however, direct evidence to support this notion is still lacking, in part, due to the lack of appropriate animal models. The overall gol of this grant proposal is to delineate the oncogenic roles of PLK1 overexpression in PCa development and metastasis. The hypothesis being tested is that PLK1 functions as a proto-oncogene during PCa initiation, progression, and metastatic dissemination. Our 2 specific aims are: 1) to define the role of PLK1 overexpression in PCa development using our recently established prostate-specific Plk1 transgenic mouse model; and 2) to determine the role of PLK1 overexpression in PCa dissemination by elucidating the molecular mechanisms underlying PLK1-induced epithelial-mesenchymal transition and PCa-cell invasion and defining the pro-metastatic properties of PLK1 using xenograft PCa models and the Plk1 transgenic mouse model. The findings of this work will provide the first in vivo evidence that PLK1 functions as a proto-oncogene in PCa. Furthermore, the results are anticipated to uncover a novel function of PLK1 that goes beyond its canonical role, and to define the oncogenic roles of PLK1 during PCa initiation, progression, and metastatic dissemination. The knowledge gained from this proposed study will fundamentally advance our understanding of the oncogenic functions of PLK1 and the molecular basis of PCa development and metastatic dissemination, which have the potential to facilitate optimization of treatment regimens targeting PLK1 signaling to significantly enhance anticancer efficacy. Furthermore, the ideas behind this proposal may be generalizable to many other cancers since preliminary clinical evidence suggests that PLK1 is involved in the development of several other human cancers.

描述（由申请人提供）：哺乳动物 Polo 样激酶 1 (PLK1) 是一种在细胞分裂的多个方面发挥关键作用的主要激酶，与人类癌症的发展密切相关，并且在各种癌症中经常过度表达，包括前列腺癌 (PCa) ). PLK1 被认为是一种原癌基因；然而，仍然缺乏支持这一观点的直接证据，部分原因是缺乏适当的动物模型。描述 PLK1 过度表达在 PCa 发展和转移中的致癌作用正在测试的假设是 PLK1 在 PCa 起始、进展和转移扩散过程中发挥原癌基因的作用。使用我们最近建立的前列腺特异性 Plk1 转基因小鼠模型来确定 PLK1 在 PCa 发育中的过度表达；2) 通过以下方法确定 PLK1 过度表达在 PCa 传播中的作用；阐明 PLK1 诱导的上皮间质转化和 PCa 细胞侵袭的分子机制，并使用异种移植 PCa 模型和 Plk1 转基因小鼠模型定义 PLK1 的促转移特性。这项工作的结果将提供第一个体内证据： PLK1 在 PCa 中充当原癌基因，此外，预计结果将揭示 PLK1 超越其典型作用的新功能，并定义其功能。 PLK1 在 PCa 起始、进展和转移扩散过程中的致癌作用从这项拟议研究中获得的知识将从根本上增进我们对 PLK1 致癌功能以及 PCa 发展和转移扩散的分子基础的理解，这有可能促进优化。此外，该提议背后的想法可能适用于许多其他癌症，因为初步临床证据表明 PLK1 参与了其他几种人类癌症的发展。癌症。