Furthermore, mechanical characteristics may serve as biomarkers for cell transformation. This is the first study to describe this novel role for caveolin-1, linking mechanical phenotype to cell transformation. 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. Caveolin-1-upregulated RhoA activity and Y397FAK phosphorylation directed actin cap formation, which was positively correlated with cell elasticity and stiffness sensing in fibroblasts. Caveolin-1, which is suppressed in many tumor cells and in oncogene-transformed cells, regulates the mechanical phenotype. Thus, cancer cells undergo a change in their mechanical phenotype that includes cell softening and loss of stiffness sensing. When cultured on matrices of varying stiffness, low stiffness decreased proliferation in normal cells, while cancer cells and transformed cells lost this response. Cancer cells were softer than their normal counterparts, regardless of the type of cancer (breast, bladder, cervix, pancreas, or Ha-Ras V12-transformed cells). Here we determined whether normal cells and cancer cells display distinct mechanical phenotypes. The stiffness sensing ability is required to respond to the stiffness of the matrix. Received: FebruAccepted: Published: Abstract
Keywords: matrix stiffness, mechanical phenotype, stiffness sensing, cell stiffness, caveolin-1 * These authors have contributed equally to this work
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 1,2ġ Department of Physiology, National Cheng Kung University, Tainan, TaiwanĢ Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwanģ Department of Biomedical Engineering, National Cheng Kung University, Tainan, TaiwanĤ Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwanĥ Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan
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