Agarwala Prema Kumari, Kapoor Shobhna
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400076, India.
J Membr Biol. 2025 Aug 18. doi: 10.1007/s00232-025-00358-z.
Aggressive cancer cells such as pancreatic cells exhibit an enhanced metastatic phenotype that involves cell migration and invasion. Cellular membrane deformation is a key process implicit in cell movement. This implicates a link between altered lipid metabolism during cancer progression and modulated membrane properties and hence associated functions. One of the key factors underlying the aggressiveness of pancreatic cancer is the presence of the highest percentage of hypoxia, which further adds to the lipid metabolic reprogramming. The subsequent effect of hypoxia-induced lipidome changes on membrane properties governing cell movement was investigated in this work using a combination of cell biology, microscopy, and spectroscopy. Our findings revealed that hypoxia induces distinct lipidome signatures in a cell-line-dependent fashion, which in turn differentially modulates the cell membrane stiffness. The correlation of cell stiffness with other membrane properties and the actin cytoskeleton shows a random correlation indicating that hypoxic stress distinctly regulates specific membrane attributes governing cellular functioning and should be consulted for the development of effective treatments for pancreatic cancer.
侵袭性癌细胞，如胰腺癌细胞，表现出增强的转移表型，涉及细胞迁移和侵袭。细胞膜变形是细胞运动中隐含的关键过程。这意味着癌症进展过程中脂质代谢改变与膜特性及相关功能调节之间存在联系。胰腺癌侵袭性的关键因素之一是存在最高比例的缺氧，这进一步加剧了脂质代谢重编程。本研究结合细胞生物学、显微镜和光谱学方法，探讨了缺氧诱导的脂质组变化对控制细胞运动的膜特性的后续影响。我们的研究结果表明，缺氧以细胞系依赖的方式诱导独特的脂质组特征，进而差异性地调节细胞膜硬度。细胞硬度与其他膜特性及肌动蛋白细胞骨架的相关性显示出随机相关性，表明缺氧应激明显调节控制细胞功能的特定膜属性，这对于开发有效的胰腺癌治疗方法具有参考价值。
