title: Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing.
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-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.
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsi-Hui
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsiu-Kuan
authors.initials: HK
authors.lastname: Lin
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chiou
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Horn-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hans I-Chen
authors.initials: HI
authors.lastname: Harn
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Chiu
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yang-Kao
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Shen
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tang
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D001696:Biomechanical Phenomena; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003094:Collagen / Q000737:chemistry; D004285:Dogs; D004548:Elasticity; D004791:Enzyme Inhibitors / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; C495540:CAV1 protein, human; D051242:Caveolin 1; D004791:Enzyme Inhibitors; C066737:RHOA protein, human; D003094:Collagen; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein
keywords: caveolin-1; cell stiffness; matrix stiffness; mechanical phenotype; stiffness sensing