Profiling fatty acid uptake and activity in single tumor cells

项目概要/摘要 分析单个肿瘤细胞中的脂肪酸摄取和活性（PI：Min Xue，UC滨江; Wei Wei，UCLA） 改变的脂肪酸代谢涉及许多类型的疾病，例如癌症。许多癌症 细胞表现出升高的脂肪酸摄取和代谢活性。在这些细胞中，脂肪酸可用作 替代能源燃料或生物质积木，以支持不受控制的增长，抵御压力， 促进转移。由于癌细胞是非常异质性的，它们对脂肪酸的摄取活动 并且预期甚至在相同的肿瘤样品内代谢也显著不同。类似于 由于脂肪酸代谢的异质性涉及其他代谢和信号传导途径， 有助于细胞的可塑性。这种变异有助于癌细胞适应营养、环境和 治疗应激，并促进耐药性和转移性病变的发展。因此 分析细胞脂肪酸代谢的能力，特别是在单细胞水平上，有望为癌症提供更多的见解 生物学在这个提议中，我们的目标是开发一种基于表面的化学方法来量化脂肪酸的摄取 以及它在单细胞中的代谢活动。我们将首先合成一组脂肪酸类似物， 细胞摄取实验，以验证它们作为评估细胞脂肪酸摄取及其相关的 代谢活动我们将采用基于表面的检测方案来量化所选择的探针。 随后，我们试图将这种检测方法纳入一个完善的基于微流体的单 细胞分析平台该工作的成功实施将为脂肪酸的分析提供一个工具 在单细胞分辨率下的酸摄取和代谢活性。此外，我们将能够执行多路复用 分析研究脂肪酸代谢和其他代谢和致癌信号之间的相互作用 途径，这可能会提供治疗的影响，不能很容易地揭示了批量水平的分析。

Project summary/Abstract Profiling fatty acid uptake and activity in single tumor cells (PIs: Min Xue, UC Riverside; Wei Wei, UCLA) Altered fatty acid metabolism is involved in many types of diseases, as exemplified in cancer. Many cancer cells exhibit elevated fatty acid uptake and metabolic activity. In these cells, fatty acids can be used as alternative energy fuels or biomass building blocks to support the uncontrolled growth, defend stress and promote metastasis. Because cancer cells are extremely heterogeneous, their activities on fatty acid uptake and metabolism are expected to vary significantly even within the same tumor sample. Similar to the heterogeneity involving other metabolic and signaling pathways, the variation in fatty acid metabolism also contribute to the cell plasticity. This variation helps cancer cells adapt to nutritional, environmental and therapeutic stress, and facilitates the development of drug resistance and metastatic lesions. Therefore, the ability to analyze cellular fatty acid metabolism, especially at single cell level, promises more insights to cancer biology. In this proposal, we aim to develop a surface-based chemical method for quantifying fatty acid uptake as well as its metabolic activities in single cells. We will first synthesize a panel of fatty acid analogs, and use cell uptake experiments to validate their utility as probes for assessing cellular fatty acid uptake and its related metabolic activities. We will employ surface-based detection schemes to quantify the selected probes. Subsequently, we seek to incorporate this detection method into a well-established microfluidics-based single cell analytical platform. Successful implementation of the proposed work will provide a tool for analyzing fatty acid uptake and metabolic activity at single cell resolution. In addition, we will be able to perform multiplexed analysis to study the interplay between fatty acid metabolism and other metabolic and oncogenic signaling pathways, which may provide therapeutic implications that cannot be easily revealed by bulk-level analysis.