Mammalian cells integrate different types of stimuli that govern their fate. These stimuli encompass biochemical as well as biomechanical cues (shear, tensile, and compressive stresses) that are usually studied separately. The phosphatidylinositol 3-kinase (PI3K) enzymes, producing signaling phosphoinositides at plasma and intracellular membranes, are key in intracellular signaling and vesicular trafficking pathways. Recent evidence in cancer research demonstrates that these enzymes are essential in mechanotransduction. Despite this, the importance of the integration of biomechanical cues and PI3K-driven biochemical signals is underestimated. In this opinion article, we make the hypothesis that modeling of biomechanical cues is critical to understand PI3K oncogenicity. We also identify known/missing knowledge in terms of isoform specificity and molecular pathways of activation, knowledge that is needed for clinical applications.

哺乳动物细胞整合了控制其命运的不同类型的刺激。这些刺激包括通常单独研究的生化和生物力学线索（剪切、拉伸和压缩应力）。磷脂酰肌醇 3-激酶 (PI3K) 酶在血浆和细胞内膜产生信号磷酸肌醇，是细胞内信号传导和水泡运输途径的关键。癌症研究的最新证据表明，这些酶在机械转导中是必不可少的。尽管如此，生物力学线索和 PI3K 驱动的生化信号整合的重要性被低估了。在这篇观点文章中，我们假设生物力学线索的建模对于理解 PI3K 致癌性至关重要。