Mechanisms of metformin-induced c-MET downregulation in triple-negative breast cancer

二甲双胍诱导三阴性乳腺癌 c-MET 下调的机制

基本信息

项目摘要

PROJECT SUMMARY Over 250,000 new cases of invasive breast cancer are expected to be diagnosed in the United States each year. Triple-negative breast cancer is a breast cancer subtype that accounts for 20% of all breast cancers diagnosed. Approximately 50,000 new cases of triple-negative breast cancer are diagnosed each year. Triple- negative breast cancer is also noted as a health disparity, being that it is most common in African-American women. Unfortunately, triple-negative breast cancer is associated with poor prognosis, often spreading to other tissues resulting in a mortality rate. This type of breast cancer is very difficult to treat because it lacks common markers targeted by cancer drugs. Therefore, scientists are developing new drugs to target molecular markers found in triple-negative breast cancers. With this, led to the testing of metformin, a drug already widely used to treat diabetes, for the treatment of triple-negative breast cancer. Interestingly, scientists discovered that fewer diabetes patients taking metformin developed cancer over time. Although metformin is safe for patients to take, the mechanism by which metformin kills cancer cells is not fully understood. The objective of this study is to investigate the mechanism of metformin-mediated c-MET regulation in its killing of basal like breast cancer (BLBC)/TNBC cells. Based on previous studies and our preliminary data, we hypothesize that downregulation of c-MET and the associated inhibition of cell proliferation and CSC self-renewal is a critical determinant of metformin-mediated inhibition of basal-like/TNBC cells. The specific aims are: 1) To determine the effects of metformin-induced c-MET inhibition on TNBC cell growth and stemness; 2) To determine the molecular mechanism of metformin-induced c-MET downregulation; and 3) To determine the impact of metformin- induced c-MET downregulation on Wnt signaling in cancer stem cell stemness inhibition. At the end of this project, we hope to have an understanding of how metformin kills triple-negative breast cancer cells and how this can be translated to future animal and human studies. In addition to research project accomplishment, I will also gain specific training in professional communication, grant writing, community outreach, and studies on cancer health disparity issues. Ultimately, the knowledge gained from our work will contribute to the elimination of cancer-related challenges associated with triple-negative breast and may be applied to other cancers to reduce the overall cancer burden.
项目概要 美国预计每年将诊断出超过 250,000 例新的浸润性乳腺癌病例 年。三阴性乳腺癌是一种乳腺癌亚型,占所有乳腺癌的 20% 确诊。每年诊断出大约 50,000 例新的三阴性乳腺癌病例。三倍- 阴性乳腺癌也被认为是一种健康差异,因为它在非裔美国人中最常见 女性。不幸的是,三阴性乳腺癌预后不良,经常扩散到其他部位 组织导致死亡率。这种类型的乳腺癌非常难以治疗,因为它缺乏常见的治疗方法。 癌症药物靶向的标记物。因此,科学家们正在开发针对分子标记的新药 发现于三阴性乳腺癌。由此,对二甲双胍进行了测试,二甲双胍是一种已经广泛用于治疗的药物 治疗糖尿病,用于治疗三阴性乳腺癌。有趣的是,科学家发现更少 服用二甲双胍的糖尿病患者随着时间的推移会患上癌症。尽管二甲双胍对患者来说是安全的, 二甲双胍杀死癌细胞的机制尚不完全清楚。本研究的目的是 研究二甲双胍介导的c-MET调节杀灭基底样乳腺癌的机制 (BLBC)/TNBC 细胞。根据之前的研究和我们的初步数据,我们假设下调 c-MET 以及相关的细胞增殖抑制和 CSC 自我更新是 C-MET 的关键决定因素 二甲双胍介导的基底细胞样/TNBC 细胞抑制。具体目标是: 1) 确定效果 二甲双胍诱导的 c-MET 对 TNBC 细胞生长和干性的抑制作用; 2)确定分子 二甲双胍诱导c-MET下调的机制; 3) 确定二甲双胍的影响 在癌症干细胞干性抑制中诱导 c-MET 对 Wnt 信号传导的下调。在这最后 项目中,我们希望了解二甲双胍如何杀死三阴性乳腺癌细胞以及如何 这可以转化为未来的动物和人类研究。除了研究项目的成果之外,我 还将获得专业沟通、资助写作、社区外展和研究方面的具体培训 关于癌症健康差异问题。最终,从我们的工作中获得的知识将有助于 消除与三阴性乳腺癌相关的癌症相关挑战,并可应用于其他 癌症,以减少总体癌症负担。

项目成果

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Dana Marie Austin Gant其他文献

Dana Marie Austin Gant的其他文献

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{{ truncateString('Dana Marie Austin Gant', 18)}}的其他基金

Mechanisms of metformin-induced c-MET downregulation in triple-negative breast cancer
二甲双胍诱导三阴性乳腺癌 c-MET 下调的机制
  • 批准号:
    10238925
  • 财政年份:
    2019
  • 资助金额:
    $ 3.51万
  • 项目类别:

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