TY - JOUR
T1 - Mechanical phenotype of cancer cells
T2 - Cell softening and loss of stiffness sensing
AU - Lin, Hsi Hui
AU - Lin, Hsiu Kuan
AU - Lin, I. Hsuan
AU - Chiou, Yu Wei
AU - Chen, Horn Wei
AU - Liu, Ching Yi
AU - Harn, Hans I.Chen
AU - Chiu, Wen Tai
AU - Wang, Yang Kao
AU - Shen, Meng Ru
AU - Tang, Ming Jer
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84940751411&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4173
DO - 10.18632/oncotarget.4173
M3 - Article
C2 - 26189182
AN - SCOPUS:84940751411
SN - 1949-2553
VL - 6
SP - 20946
EP - 20958
JO - Oncotarget
JF - Oncotarget
IS - 25
ER -