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Role of LMPTP in Prostate Cancer

LMPTP 在前列腺癌中的作用

基本信息

批准号：
10198250
负责人：
Stephanie Stanford
金额：
$ 42.19万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198250
关键词：
Address American Androgen Receptor Attention Bioavailable Biochemical Biology CRISPR/Cas technology Cancer Cell Growth Cancer Etiology Cancer Patient Castration Cessation of life Chemicals Data Disseminated Malignant Neoplasm Extracellular Matrix Generations Genes Glycogen Synthase Kinase 3 Goals Growth Health Human Impairment In Vitro Insulin Antagonists Insulin Receptor Insulin Resistance Knock-out Liver Malignant Neoplasms Malignant neoplasm of prostate Mediating Medical Metastatic Neoplasm to the Bone Metastatic Prostate Cancer Modeling Molecular Molecular Weight Mus Neoplasm Metastasis Nuclear Translocation Obesity Operative Surgical Procedures Oral Pathway interactions Patient-Focused Outcomes Patients Pharmacological Treatment Pharmacology Phosphorylation Positioning Attribute Prognostic Factor Property Prostate Prostate Adenocarcinoma Prostate Cancer therapy Prostatic Neoplasms Protein Dephosphorylation Protein Tyrosine Phosphatase Proto-Oncogene Proteins c-akt Receptor Activation Receptor Signaling Recurrence Reporting Research Personnel Resistance Resources Role Signal Pathway Signal Transduction Surveys Systemic Therapy The Cancer Genome Atlas Time Transactivation Tumor Tissue Tyrosine Validation Vertebral column Xenograft Model Xenograft procedure advanced prostate cancer androgen deprivation therapy bone castration resistant prostate cancer cell growth growth promoting activity high reward high risk improved outcome in vivo inhibitor/antagonist men new therapeutic target novel novel therapeutics overexpression phosphatase inhibitor promoter prostate cancer cell prostate cancer cell line prostate cancer model tumor growth tumorigenesis

项目摘要

ABSTRACT The objective of this proposal is to perform exploratory examination of the low molecular weight protein tyrosine phosphatase (LMPTP) as a new target for prostate cancer therapy. Prostate cancer is among the leading causes of cancer death in American men, and novel therapies to inhibit prostate tumor growth and metastasis are a major unmet medical need in cancer. LMPTP is a tyrosine phosphatase encoded by the ACP1 gene. Several recent reports have demonstrated that LMPTP is overexpressed in human prostate tumors, and that LMPTP expression associates with post-surgical biochemical recurrence and shorter patient survival time. Since little was known about the role of LMPTP in tumor growth, we decided to investigate the role of LMPTP in prostate cancer cells. We generated prostate cancer cell lines carrying LMPTP knockout (KO), and found that loss of LMPTP significantly impaired their proliferation, colony formation, and invasiveness in vitro. We also found that LMPTP is a key promoter of prostate tumor growth in vivo. We have additional preliminary data demonstrating that LMPTP promotes activation of the androgen receptor in prostate cancer cells. Here, our goal is to gain exploratory evidence of the potential for LMPTP as a novel target for prostate cancer therapy. We seek to determine the molecular mechanism by which LMPTP promotes prostate cancer cell growth (Aim 1) and to demonstrate that pharmacological LMPTP inhibition reverses castration- resistant prostate tumor growth and impairs prostate tumor bone metastasis (Aim 2). Our project is exploratory, high-risk, and has a clear translational perspective for prostate cancer. We will pursue this project using unique resources that we have developed, including a novel patient-derived bone metastasis model for prostate cancer and a newly developed LMPTP inhibitor with excellent pharmacological properties. We are uniquely positioned to succeed in this study and are excited to uncover the potential of LMPTP as a novel target for prostate cancer therapy.

摘要