Chloe Simpson, Vignesh Sundararajan, Tuan Zea Tan, Ruby Huang, Michael Sheetz*
Cancer cells have many different behaviors from epithelial to mesenchyme forms. We report here that 36 distinct tumor cell lines regardless of EMT form or other features lack the ability to sense rigidity and will grow on soft surfaces. In the majority of lines, cells were missing at least one protein needed for rigidity sensing (primarily tropomyosin 2.1 (Tpm2.1) but also PTPN12, FilaminA (FLNA), and myosin IIA) while all had high levels of Tpm3. In the few cases where the major rigidity sensing components were present, those tumor cells were not able to sense rigidity. Thus, we suggest that tumor cells can lose the ability to sense rigidity by many different means and that the loss of rigidity sensing is sufficient to cause the transformed phenotype that enables targeted treatments.