探索预防癌症进展的工具需要理解正常细胞与癌细胞之间的根本差异。十多年前，原子力显微镜（AFM）揭示了癌细胞与其健康对应物相比的较软的体质。在这里，我们通过AFM高分辨率硬度层析成像和三维共聚焦显微镜研究了癌细胞软化相对于其健康对应物的机制。我们展示了浸润性导管癌细胞细胞骨架中微管（MTs）网络位于基底位置，并与细胞周边分段约400nm。此外，细胞骨架支架蛋白质plectin在癌症细胞中从细胞质错位到细胞表面，从而解释了MT网络与细胞皮质的解离。此外，在高分辨率AFM图像中使用蠕虫链（WLC）模型评估MTs的持久长度显示，与正常状态相比，导管癌中单个MTs的持久长度较低。总的来说，这些调整后的机械特性支持侵袭性细胞在小变形下承受更大的压缩力。这些数据提供了癌症进展的结构起源的新见解。

Discovering tools to prevent cancer progression requires understanding the fundamental differences between normal and cancer cells. More than a decade ago, atomic force microscopy (AFM) revealed cancer cells' softer body compared to their healthy counterparts. Here, we investigated the mechanism underlying the softening of cancerous cells in comparison with their healthy counterparts based on AFM high resolution stiffness tomography and 3D confocal microscopy. We showed microtubules (MTs) network in invasive ductal carcinoma cell cytoskeleton is basally located and segmented for around 400 nm from the cell periphery. Additionally, the cytoskeleton scaffolding protein plectin exhibits a mis-localization from the cytoplasm to the surface of cells in the carcinoma which justifies the dissociation of the MT network from the cell's cortex. Furthermore, the assessment of MTs' persistence length using a worm-like-chain (WLC) model in high resolution AFM images showed lower persistence length of the single MTs in ductal carcinoma compared to that in the normal state. Overall, these tuned mechanics support the invasive cells to ascertain more flexibility under compressive forces in small deformations. These data provide new insights into the structural origins of cancer aids in progression.