Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing

// Hsi-Hui Lin 1* , Hsiu-Kuan Lin 2* , I-Hsuan Lin 1 , Yu-Wei Chiou 3 , Horn-Wei Chen 1 , Ching-Yi Liu 2 , Hans I-Chen Harn 2 , Wen-Tai Chiu 3 , Yang-Kao Wang 4 , Meng-Ru Shen 5 and Ming-Jer Tang 1,2 1 Department of Physiology, National Cheng Kung University, Tainan, Taiwan 2 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 3 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan 4 Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan 5 Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan * These authors have contributed equally to this work Correspondence to: Ming-Jer Tang, email: // Keywords : matrix stiffness, mechanical phenotype, stiffness sensing, cell stiffness, caveolin-1 Received : February 20, 2015 Accepted : May 02, 2015 Published : May 19, 2015 Abstract The stiffness sensing ability is required to respond to the stiffness of the matrix. Here we determined whether normal cells and cancer cells display distinct mechanical phenotypes. Cancer cells were softer than their normal counterparts, regardless of the type of cancer (breast, bladder, cervix, pancreas, or Ha-Ras V12 -transformed cells). When cultured on matrices of varying stiffness, low stiffness decreased proliferation in normal cells, while cancer cells and transformed cells lost this response. Thus, cancer cells undergo a change in their mechanical phenotype that includes cell softening and loss of stiffness sensing. Caveolin-1, which is suppressed in many tumor cells and in oncogene-transformed cells, regulates the mechanical phenotype. Caveolin-1-upregulated RhoA activity and Y397 FAK phosphorylation directed actin cap formation, which was positively correlated with cell elasticity and stiffness sensing in fibroblasts. Ha-Ras V12 -induced transformation and changes in the mechanical phenotypes were reversed by re-expression of caveolin-1 and mimicked by the suppression of caveolin-1 in normal fibroblasts. This is the first study to describe this novel role for caveolin-1, linking mechanical phenotype to cell transformation. Furthermore, mechanical characteristics may serve as biomarkers for cell transformation.