Abstract：
Cell-cell interactions, which allow cells to communicate with each other through molecules in their microenvironment, are critical for the growth, health, and functions of cells. Previous studies show that drug-resistant cells can interact with drug-sensitive cells to elevate their drug resistance level, which is partially responsible for cancer recurrence. Studying protein targets and pathways involved in cell-cell communication provides essential information for fundamental cell biology studies and therapeutics of human diseases. In the current studies, we performed direct coculture and indirect coculture of drug-resistant and drug-sensitive cell lines, aiming to investigate intracellular proteins responsible for cell communication. Comparative studies were carried out using monoculture cells. Shotgun bottom-up proteomics results indicate that the P53 signaling pathway has a strong association with drug resistance mechanisms, and multiple TP53-related proteins were upregulated in both direct and indirect coculture systems. In addition, cell-cell communication pathways, including the phagosome and the HIF-signaling pathway, contribute to both direct and indirect coculture systems. Consequently, AK3 and H3-3A proteins were identified as potential targets for cell-cell interactions that are relevant to drug resistance mechanisms. We propose that the P53 signaling pathway, in which mitochondrial proteins play an important role, is responsible for inducing drug resistance through communication between drug-resistant and drug-sensitive cancer cells.
摘要：
细胞间的相互作用，允许细胞通过微环境中的分子相互交流，对增长至关重要，健康,和细胞的功能。先前的研究表明，耐药细胞可以与药物敏感细胞相互作用，从而提高其耐药水平，这是癌症复发的部分原因。研究参与细胞-细胞通讯的蛋白质靶标和途径为基础细胞生物学研究和人类疾病的治疗提供了必要的信息。在目前的研究中,我们进行了耐药和药物敏感细胞系的直接共培养和间接共培养，旨在研究负责细胞通讯的细胞内蛋白质。使用单一培养细胞进行比较研究。Shotgun自下而上的蛋白质组学结果表明，P53信号通路与耐药机制具有很强的相关性，在直接和间接共培养系统中，多种TP53相关蛋白上调。此外,细胞-细胞通讯通路，包括吞噬体和HIF信号通路，有助于直接和间接共培养系统。因此,AK3和H3-3A蛋白被鉴定为与耐药机制相关的细胞-细胞相互作用的潜在靶标。我们认为P53信号通路,线粒体蛋白在其中发挥重要作用，负责通过耐药和药物敏感的癌细胞之间的通讯诱导耐药性。
