Tensin regulation of tumour cell movement: a link between metabolism and motility

癌细胞主要通过糖酵解过程产生能量。在正常细胞中，这通常只发生在氧气供应有限的情况下，但癌细胞优先使用这一途径，即使在氧气存在的情况下（有氧糖酵解）。由于这是一种低效的产生能量的途径，因此对于这赋予肿瘤细胞的优势存在一些争论，但人们认为，它通过产生细胞分裂所需的分子，为肿瘤细胞提供了生长优势。通过使用正电子发射断层扫描（PET）检测肿瘤，癌细胞代谢对患者管理的潜在影响已得到证实。然而，越来越清楚的是，肿瘤细胞的糖酵解性质可能会改变细胞功能，而不仅仅是检测的标记。最近我们发现癌细胞中的有氧糖酵解促进细胞侵袭，这可能与肿瘤代谢改变与肿瘤扩散有关。癌细胞的运动性尤其具有重要意义，因为癌细胞扩散到局部组织（侵袭）或身体其他部位（转移）需要运动性。癌细胞在组织中的移动需要与细胞外基质（ECM）相互作用，而这是通过细胞表面专门的整合素受体来调节的。我们感兴趣的是一种叫做Tensin的分子，它可以将整合素与细胞内的支架（结构）蛋白连接起来。我们发现，tensin不仅仅作为一种结构支持，还在癌细胞运动中发挥作用，并且这些分子的表达可以通过细胞代谢来调节；癌细胞中的有氧糖酵解导致代谢传感器（CtBP2蛋白）的激活，该传感器控制着Tensin的水平。反过来，这影响了癌细胞粘附和/或在ECM上移动的方式，并在代谢和运动之间提供了一种新的联系。通过研究肿瘤代谢、tensin和细胞外基质相互作用之间的关系，我们希望找到代谢传感和信号通路中的关键靶点，进一步了解肿瘤细胞侵袭和转移的调节机制，并可能找到新的诊断和治疗靶点。我是一名耳鼻喉科(ENT)/头颈外科的三年级实习生，我非常希望使用分子生物学技术来彻底改变我们治疗癌症的方法。这项研究是在南安普顿大学的英国卓越中心进行的，涉及两个国际公认的领先团队在这些学科的综合研究专长。在这项研究中，我将掌握的方法和技术包括各种基于细胞的分析，这不仅是我未来学术生涯的关键，而且还将使外科社区的关键研究技能得到发展。我热衷于推动科学与外科之间的合作。

Cancer cells generate their energy mostly through a process known as glycolysis. In normal cells this only usually occurs when oxygen supply is limited, but cancer cells use this pathway preferentially, even when oxygen is present (aerobic glycolysis). There is some debate as to the advantage this confers to tumour cells, since it is an inefficient pathway for generating energy, but it is thought that it provides tumour cells with a growth advantage by generating molecules required for cell division. The potential for cancer cell metabolism to impact on patient management has been shown through the use of positron emission tomography (PET) for the detection of tumours. However, it is becoming clear that rather than being simply a marker for detection, a tumour cell's glycolytic nature may alter cell function. Recently we have found that aerobic glycolysis in cancer cells promotes cell invasion, and this may link altered tumour metabolism with tumour spread. Motility in cancer cells in particular has great significance, as it is required for cancer cells to spread either into local tissues (invasion) or other parts of the body (metastasis). Movement through tissues requires cancer cells to interact with the extracellular matrix (ECM), and this is regulated through specialised integrin receptors on the cell surface. We are interested in a molecule called Tensin, which serves to link integrins to scaffolding (structural) proteins inside the cell. Far from acting solely as a structural support, we have found that Tensins play a role in cancer cell movement, and that expression of these molecules can be regulated by cell metabolism; aerobic glycolysis in cancer cells results in the activation of a metabolic sensor (CtBP2 protein), which controls the level of Tensin. In turn, this affects the way in which cancer cells adhere and/or move on the ECM and provides a novel link between metabolism and motility. Through our work exploring the relationship between tumour metabolism, Tensins and extracellular matrix interactions, we hope to identify key targets in the metabolic sensing and signalling pathways, furthering our understanding of the mechanisms regulating tumour cell invasion and metastasis, and possibly enabling the identification of new diagnostic and therapeutic targets.I am a 3rd year otolaryngology (ENT)/head & neck surgical trainee, with a strong desire to use molecular biology techniques to revolutionise our approach to cancer. This research is being performed in a UK centre of excellence at the University of Southampton, and involves the combined research expertise of two Internationally recognised leading groups in these disciplines. The methods and techniques that I will master during this research include a variety of cell-based assays and will be key not only for my future academic career, but will also enable the development of key research skills within the surgical community. I am passionate to drive this collaboration between science and surgery forward.