Cancer Cells in all EMT States Lack Rigidity Sensing Depletion of Different Tumor Suppressors Causes Loss of Rigidity Sensing in Cancer Cells

Abstract

Cancer cells have many different behaviors from epithelial to mesenchymal 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 tropomyosin2.1 (Tpm2.1) but also PTPN12, FilaminA (FLNA), and myosinIIA) 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.

Cancer cells can be killed mechanically or with combinations of cytoskeletal inhibitors

“…These behaviors have proven true for a number of tumor and normal cells across different tissues ( Yang et al, 2020 ; Tijore et al, 2021 ). For example, in a screen of 36 ovarian tumor cell lines ranging from epithelial to mesenchymal, they all appear to lack early rigidity sensing, with most cell lines missing known components of the rigidity sensor (half of the cell lines are depleted in tropomyosin 2.1) ( Simpson et al, 2022 ).…”