mda-9/svntenin: A Novel Diagnostic Marker and a Therapeutic Target for Metastatic

mda-9/svntenin：一种新型诊断标记物和转移性治疗靶点

基本信息

批准号：
8121510
负责人：
DEVANAND SARKAR
金额：
$ 4.99万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8121510
关键词：
Adjuvant Therapy Biology Breast Categories Caucasians Caucasoid Race Cell Adhesion Correlation Studies Development Diagnostic Disease Disseminated Malignant Neoplasm Genes Growth Guidelines Human Incidence Malignant Neoplasms Mediating Melanoma Cell Metastatic Melanoma Modality Neoplasm Metastasis Nude Mice Phenotype Play Population Prognostic Marker Property Proteins Qualifying Radiation therapy Refractory Research Personnel Resistance Role Services Signal Transduction Signal Transduction Pathway Site Skin Skin Cancer Small Interfering RNA Staging Subfamily lentivirinae Therapeutic Therapeutic Intervention Thick Xenograft procedure adapter protein base cancer cell chemotherapy conventional therapy improved malignant stomach neoplasm melanoma metastatic process migration novel diagnostics novel marker outcome forecast overexpression prognostic research study response therapeutic target tool

项目摘要

Melanoma is a type of skin cancer whose incidence has steadily risen particularly in the Caucasian population over the last few decades. In the advanced stages of the disease, melanomas are characterized with a high metastatic potential, are extremely refractory to adjuvant therapies like radio- or chemotherapy and are often fatal. These observations underscore the need for developing novel markers indicative of metastatic potential and improved treatment modalities targeting the metastatic component of the disease. Melanoma differentiation associated gene-9 (mda-9), also known as syntenin, is an adapter molecule that plays important roles in diverse cell signaling mechanisms. Recent experiments document an association of mda-9/syntenin with metastatic cancers. A gradual increase in mda-9/syntenin expression level was observed with the progression of melanomas and overexpression of mda-9/syntenin in poorly metastatic breast or gastric cancer cells increased their invasion and migration properties. Inhibition of mda-9/syntenin by siRNA suppressed the invasive phenotype of aggressive melanoma cells indicating that mda-9/syntenin might play a key role in mediating the metastatic process. Based on these findings, the studies in this proposal will determine the significance of mda-9/syntenin in melanoma progression through the following specific aims: i) To correlate changes in mda-9/syntenin expression with different stages of human melanoma, ii) To analyze the effect of overexpresssion of mda-9/syntenin on poorly metastatic melanomas and iii) To target mda-9/syntenin as a potential therapeutic intervention for metastatic melanomas. Successful completion of these studies will facilitate the understanding of mda-9/syntenin in melanoma metastasis and its development as a diagnostic and/or prognostic tool and a therapeutic target for metastatic melanomas.Dr. Sarkar qualifies as Category #1 in the Guidelines as a New Investigator with extensive expertise in melanoma biology. This P&F study will utilize the services of Cores A, B, C, and D.

黑色素瘤是一种皮肤癌，其发病率稳步上升，尤其是在白种人中过去几十年的人口。在疾病的晚期阶段，黑色素瘤的特征是具有高转移潜力，对放疗或化疗等辅助疗法极难治疗并且往往是致命的。这些观察结果强调需要开发新的标记来指示转移潜力和针对疾病转移成分的改进治疗方式。黑色素瘤分化相关基因 9 (mda-9)，也称为 Syntenin，是一种接头分子，在多种细胞信号传导机制中发挥着重要作用。最近的实验记录了以下关联： mda-9/syntenin 与转移性癌症。 mda-9/syntenin 表达水平逐渐增加观察到黑色素瘤的进展和转移不良的 mda-9/syntenin 的过度表达乳腺癌或胃癌细胞增强了其侵袭和迁移特性。 mda-9/syntenin 的抑制通过 siRNA 抑制侵袭性黑色素瘤细胞的侵袭表型，表明 mda-9/syntenin 可能在介导转移过程中发挥关键作用。基于这些发现，本研究该提案将通过以下方式确定 mda-9/syntenin 在黑色素瘤进展中的重要性具体目标： i) 将 mda-9/syntenin 表达的变化与人类不同阶段相关联黑色素瘤，ii) 分析 mda-9/syntenin 过表达对转移性较差的黑色素瘤的影响 iii) 将 mda-9/syntenin 靶向作为转移性黑色素瘤的潜在治疗干预措施。这些研究的成功完成将有助于理解黑色素瘤中的 mda-9/syntenin 转移及其作为诊断和/或预后工具以及转移治疗靶点的发展黑色素瘤。博士。萨卡 (Sarkar) 作为一名新研究者，符合指南中的第 1 类资格，具有广泛的研究经验。黑色素瘤生物学方面的专业知识。本 P&F 研究将利用核心 A、B、C 和 D 的服务。