Monitoring Partial EMT Dynamics through Cell Mechanics Using Scanning Ion Conductance Microscopy

Tumor cells undergo an epithelial-mesenchymal transition (EMT) accompanied by a reduction in elasticity to initiate metastasis. However, <i>in vivo</i>, tumor cells typically exhibit partial EMT rather than fully EMT. Whether cell mechanics can accurately identify the status of partial EMT, especially the dynamic process, remains unclear. To elucidate the relationship between cell mechanics and partial EMT, we employed scanning ion conductance microscopy (SICM) to analyze the dynamic changes in cell mechanics during the TGFβ-induced partial EMT of HCT116 colon cancer cells. Cells undergoing partial EMT, characterized by increased expression of EMT transcription factors, <i>Snai1</i> and <i>Zeb1</i>, and EMT-related genes, <i>Fn1</i> and <i>MMP9</i>, while retaining the expression of the epithelial markers <i>E</i>-<i>cadherin</i> (<i>E</i>-<i>cad</i>) and <i>EpCAM</i>, did not exhibit significant changes in cell morphology, suggesting that morphological changes alone were inadequate for identifying partial EMT status. However, cell elasticity markedly decreased in partial EMT cells, and this reduction was reversed with the reversible transition of partial EMT. These findings suggest a strong correlation between cell mechanics and the dynamic process of partial EMT, indicating that cell mechanics could serve as a valuable label-free marker for identifying the status of partial EMT while preserving the physiological characteristics of tumor cells.