A2: PROJ 1: LYSYL OXIDASE-LIKE 2 (LOXL2) IN CANCER CELL INVASION

A2：项目 1：赖氨酰氧化酶样 2 (LOXL2) 在癌细胞侵袭中的作用

• 批准号: 7336063
• 负责人: SHERI F T FONG
• 金额: $ 5.63万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-17 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7336063
• 关键词: amine oxidoreductase; breast neoplasms; cell line; neoplasm /cancer; neoplastic cell; proteins

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer is responsible for one in four deaths in the United States, the second most common cause of mortality. Most of the morbidity and mortality caused by cancer can be attributed to metastasis, the spread or movement of cancer cells from its origin to other areas of the body. Two of the earliest requirements in metastasis are that cancer cells must be able to move (migrate), and then break through the meshwork of molecules surrounding the cells (invade) to be able to spread to different areas of the body. If one can understand the mechanisms that contribute to cancer cell migration and invasion, one has a potential drug target that may impede or eliminate cancer growth and spread. The focus of this project is to characterize the role of the lysyl oxidase like-2 (LOXL2) protein in cancer cell migration and invasion. We have looked at many cancer tissues and found that the tissues with more LOXL2 protein are associated with markers of poorer prognosis. We have shown that the LOXL2 protein is only present in highly invasive/ metastatic breast cancer cell lines. Poorly invasive/non-metastatic breast cancer cell lines have no LOXL2 protein. We have developed poorly invasive/non-metastatic breast cancer cell lines which permanently produce LOXL2 protein in order to evaluate if the presence of LOXL2 will enable the cells to migrate and invade through a synthetic meshwork of molecules called Matrigel. We will also silence the expression of LOXL2 in highly invasive/metastatic breast cancer cell lines to evaluate if the absence of LOXL2 will render the cells unable to migrate or invade. We will also evaluate if catalytic activity and certain protein domains are important in the role of LOXL2 in migration and invasion.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。在美国，癌症造成四分之一的死亡，是第二大常见死因。癌症引起的大多数发病率和死亡率可归因于转移，即癌细胞从其起源扩散或移动到身体的其他部位。转移的两个最早的要求是癌细胞必须能够移动（迁移），然后突破细胞周围的分子网络（入侵），以便能够扩散到身体的不同区域。如果人们能够了解促进癌细胞迁移和侵袭的机制，就可以找到一个可能阻止或消除癌症生长和扩散的潜在药物靶点。该项目的重点是表征赖氨酰氧化酶样 2 (LOXL2) 蛋白在癌细胞迁移和侵袭中的作用。我们研究了许多癌症组织，发现含有较多 LOXL2 蛋白的组织与预后较差的标志物相关。我们已经证明 LOXL2 蛋白仅存在于高度侵袭性/转移性乳腺癌细胞系中。侵袭性差/非转移性乳腺癌细胞系没有 LOXL2 蛋白。我们开发了侵袭性差/非转移性乳腺癌细胞系，它们永久产生 LOXL2 蛋白，以评估 LOXL2 的存在是否将使细胞能够通过称为基质胶的分子合成网络迁移和侵袭。我们还将沉默高侵袭性/转移性乳腺癌细胞系中 LOXL2 的表达，以评估 LOXL2 的缺失是否会导致细胞无法迁移或侵袭。我们还将评估催化活性和某些蛋白质结构域对于 LOXL2 在迁移和侵袭中的作用是否重要。