Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing
Metrics: PDF 2780 views | HTML 3179 views | ?
Hsi-Hui Lin1*, Hsiu-Kuan Lin2*, I-Hsuan Lin1, Yu-Wei Chiou3, Horn-Wei Chen1, Ching-Yi Liu2, Hans I-Chen Harn2, Wen-Tai Chiu3, Yang-Kao Wang4, Meng-Ru Shen5 and Ming-Jer Tang1,2
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
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
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-RasV12-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 Y397FAK phosphorylation directed actin cap formation, which was positively correlated with cell elasticity and stiffness sensing in fibroblasts. Ha-RasV12-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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.