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

Hsi Hui Lin, Hsiu Kuan Lin, I. Hsuan Lin, Yu Wei Chiou, Horn Wei Chen, Ching Yi Liu, Hans I.Chen Harn, Wen Tai Chiu, Yang Kao Wang, Meng Ru Shen, Ming Jer Tang

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20946-20958
Number of pages13
JournalOncotarget
Volume6
Issue number25
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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