'Definition of the mechanisms sensing viscosity in pancreatic cancer'

“胰腺癌中感知粘度的机制的定义”

• 批准号: 2898118
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2898118
• 关键词: Definition; mechanisms; sensing; viscosity; pancreatic

"The behaviour of cells is determined by how they interpret their genetic and epigenetic programming in the context of signals from their surroundings. These environmental cues are often chemical, but recent work has shown the importance of mechanical stimulation in driving responses to cell morphology, metabolism, motility, proliferation and commitment to lineage. More recently, variations in viscosity of the extracellular environment, as well as its rigidity, have been demonstrated to modulate cell signalling and alter phenotypic responses. However, very little is known about the mechanisms of viscosity sensing. Cells sense the mechanical properties of their environment through integrin adhesion receptors that bind and pull against components of the extracellular matrix (ECM). The modulated response to ECM stiffness, and its maintenance at the appropriate level, is essential for tissue health. The ECM is also central to many disease processes, and the aberrantly stiff, fibrotic environment of many cancers has been shown to contribute to uncontrolled cellular proliferation and metastatic processes. In pancreatic ductal adenocarcinoma (PDAC), for example, the ECM produced by pancreatic fibroblasts (PFs) is an order of magnitude stiffer than the healthy tissue. "

“细胞的行为取决于它们如何在来自周围环境的信号的背景下解释其遗传和表观遗传编程。这些环境线索通常是化学的，但最近的工作表明，机械刺激在驱动细胞形态，代谢，运动，增殖和谱系承诺的反应中的重要性。最近，已经证明细胞外环境的粘度以及其刚性的变化可以调节细胞信号传导并改变表型反应。然而，很少有人知道的粘度传感的机制。细胞通过整合素粘附受体感知其环境的机械特性，所述整合素粘附受体结合并拉动细胞外基质（ECM）的组分。对ECM硬度的调制响应及其在适当水平的维持对于组织健康是必不可少的。ECM也是许多疾病过程的核心，并且许多癌症的异常僵硬的纤维化环境已被证明有助于不受控制的细胞增殖和转移过程。例如，在胰腺导管腺癌（PDAC）中，由胰腺成纤维细胞（PF）产生的ECM比健康组织硬一个数量级。"