Elucidating the Role of UCHL1 in Aggressive Prostate Cancer

阐明 UCHL1 在侵袭性前列腺癌中的作用

• 批准号: 10652457
• 负责人: Tanya I Stoyanova
• 金额: $ 34.98万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652457
• 关键词: Advanced Development; Aggressive Clinical Course; Androgens; Animal Model; Biological Assay; Biological Models; Biotin; Cancer Etiology; Castration; Cell Line; Cells; Cessation of life; Development; Disease; Down-Regulation; Goals; Growth; Human; Incidence; Life Expectancy; Malignant neoplasm of prostate; Mass Spectrum Analysis; Mediating; Metastatic Prostate Cancer; Modeling; Molecular; Neoplasm Metastasis; Neurosecretory Systems; Pathway interactions; Patients; Peptide Hydrolases; Proteins; Proteome; Proteomics; Recurrence; Regulation; Relapse; Research; Resistance; Role; Sampling; Series; Signal Transduction; Study Section; Testing; Therapeutic; Therapeutic Intervention; Time; UCHL1 gene; UCHL1 protein; Ubiquitin; United States; Xenograft Model; advanced disease; advanced prostate cancer; aggressive therapy; androgen deprivation therapy; castration resistant prostate cancer; combat; hormone therapy; inhibitor; insight; men; mortality; neuroendocrine phenotype; novel; novel therapeutic intervention; overexpression; patient derived xenograft model; pre-clinical; preclinical study; prostate cancer cell line; prostate cancer metastasis; prostate cancer model; protein degradation; response; therapeutic candidate; therapeutic evaluation; therapeutic target; therapy resistant; tumor; tumor growth; ubiquitin C-terminal hydrolase

PROJECT SUMMARY/ABSTRACT Prostate cancer is the second leading cause of cancer associated deaths in men in the United States. The first line of treatment for men with advanced metastatic prostate cancer is hormone therapy. Although initial responses are observed, unfortunately, the disease commonly recurs in its aggressive hormone therapy- resistant form, which is largely responsible for prostate cancer-specific mortality. Thus, there is an urgent need to define the mechanisms that drive the aggressive disease. We have recently shown that UCHL1 protein is implicated in regulating aggressive prostate cancer growth and prostate cancer metastasis. We have strong preliminary evidence suggesting that UCHL1 may be a new promising therapeutic target for aggressive prostate cancer. We have recently demonstrated that inhibition of UCHL1 suppresses prostate cancer growth. The main goals of the proposed project are: 1) test the functional role of UCHL1 in advanced prostate cancer. 2) investigate the molecular mechanism through which UCHL1 signals in aggressive prostate cancer. 3) test the therapeutic potential of UCHL1 inhibition in animal models of aggressive disease and patient-derived xenografts in preclinical settings. Successful completion of the proposed research will lead to: 1) defining the role of UCHL1 in aggressive therapy- resistant prostate cancer, 2) the discovery of new molecular mechanisms underlying UCHL1 function and the development of aggressive prostate cancer which will guide us towards novel therapeutic strategies to target the advanced disease and 3) direct new strategies regarding novel therapeutic interventions to combat the deadly form of the disease.

项目总结/摘要 前列腺癌是美国男性癌症相关死亡的第二大原因。第一 晚期转移性前列腺癌的治疗线是激素疗法。尽管最初 不幸的是，这种疾病通常在其积极的激素治疗中复发- 耐药形式，这在很大程度上负责前列腺癌特异性死亡率。因此，迫切需要 来确定这种侵袭性疾病的发病机制。 我们最近发现UCHL 1蛋白参与调节侵袭性前列腺癌的生长， 前列腺癌转移我们有强有力的初步证据表明，UCHL 1可能是一种新的 有希望的治疗靶点。我们最近已经证明， UCHL 1抑制前列腺癌生长。 拟议项目的主要目标是： 1)测试UCHL 1在晚期前列腺癌中的功能作用。 2)研究UCHL 1信号在侵袭性前列腺癌中的分子机制。 3)在侵袭性疾病的动物模型和患者来源的 临床前环境中的异种移植物。 拟议研究的成功完成将导致：1）定义UCHL 1在积极治疗中的作用- 耐药前列腺癌，2）发现UCHL 1功能的新分子机制， 发展的侵袭性前列腺癌，这将指导我们对新的治疗策略，以靶向 3）指导关于新的治疗干预措施的新战略，以对抗致命的 疾病的形式。

项目成果

Metastasis Model to Test the Role of Notch Signaling in Prostate Cancer.

测试Notch信号在前列腺癌中的作用的转移模型。

• DOI: 10.1007/978-1-0716-2201-8_18
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Liu,Shiqin;Hsu,En-Chi;Shen,Michelle;Aslan,Merve;Stoyanova,Tanya
• 通讯作者: Stoyanova,Tanya

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer.

• DOI: 10.1038/s41416-020-01200-0
• 发表时间: 2021-03
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Liu S;Shen M;Hsu EC;Zhang CA;Garcia-Marques F;Nolley R;Koul K;Rice MA;Aslan M;Pitteri SJ;Massie C;George A;Brooks JD;Gnanapragasam VJ;Stoyanova T
• 通讯作者: Stoyanova T

Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay.

通过高型免疫测定法发现了CASP8作为高风险前列腺癌的潜在生物标志物。

• DOI: 10.1038/s41598-021-87155-5
• 发表时间: 2021-04-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Liu S;Garcia-Marques F;Zhang CA;Lee JJ;Nolley R;Shen M;Hsu EC;Aslan M;Koul K;Pitteri SJ;Brooks JD;Stoyanova T
• 通讯作者: Stoyanova T

Protein signatures to distinguish aggressive from indolent prostate cancer.

• DOI: 10.1002/pros.24307
• 发表时间: 2022-04
• 期刊: The Prostate
• 作者: Garcia-Marques F;Liu S;Totten SM;Bermudez A;Tanimoto C;Hsu EC;Nolley R;Hembree A;Stoyanova T;Brooks JD;Pitteri SJ
• 通讯作者: Pitteri SJ

In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.

• DOI: 10.1158/0008-5472.can-20-2969
• 发表时间: 2021-05-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Xie J;Rice MA;Chen Z;Cheng Y;Hsu EC;Chen M;Song G;Cui L;Zhou K;Castillo JB;Zhang CA;Shen B;Chin FT;Kunder CA;Brooks JD;Stoyanova T;Rao J
• 通讯作者: Rao J