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-Gao Wang, Meng-Ru Shen, Ming-Jer Tang

Research output: Contribution to journalArticle

49 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 Jan 1

Fingerprint

Phenotype
Caveolin 1
Neoplasms
Fibroblasts
Elasticity
Oncogenes
Urinary Bladder Neoplasms
Cervix Uteri
Actins
Pancreas
Biomarkers
Phosphorylation
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Lin, H. H., Lin, H. K., Lin, I. H., Chiou, Y. W., Chen, H. W., Liu, C. Y., ... Tang, M-J. (2015). Mechanical phenotype of cancer cells: Cell softening and loss of stiffness sensing. Oncotarget, 6(25), 20946-20958. https://doi.org/10.18632/oncotarget.4173
Lin, Hsi Hui ; Lin, Hsiu Kuan ; Lin, I. Hsuan ; Chiou, Yu Wei ; Chen, Horn Wei ; Liu, Ching Yi ; Harn, Hans I.Chen ; Chiu, Wen-Tai ; Wang, Yang-Gao ; Shen, Meng-Ru ; Tang, Ming-Jer. / Mechanical phenotype of cancer cells : Cell softening and loss of stiffness sensing. In: Oncotarget. 2015 ; Vol. 6, No. 25. pp. 20946-20958.
@article{7577eb0c0af9409aa4e6896003be3abe,
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.",
author = "Lin, {Hsi Hui} and Lin, {Hsiu Kuan} and Lin, {I. Hsuan} and Chiou, {Yu Wei} and Chen, {Horn Wei} and Liu, {Ching Yi} and Harn, {Hans I.Chen} and Wen-Tai Chiu and Yang-Gao Wang and Meng-Ru Shen and Ming-Jer Tang",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.4173",
language = "English",
volume = "6",
pages = "20946--20958",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "25",

}

Mechanical phenotype of cancer cells : Cell softening and loss of stiffness sensing. / Lin, Hsi Hui; Lin, Hsiu Kuan; Lin, I. Hsuan; Chiou, Yu Wei; Chen, Horn Wei; Liu, Ching Yi; Harn, Hans I.Chen; Chiu, Wen-Tai; Wang, Yang-Gao; Shen, Meng-Ru; Tang, Ming-Jer.

In: Oncotarget, Vol. 6, No. 25, 01.01.2015, p. 20946-20958.

Research output: Contribution to journalArticle

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-Gao

AU - Shen, Meng-Ru

AU - Tang, Ming-Jer

PY - 2015/1/1

Y1 - 2015/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84940751411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940751411&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.4173

DO - 10.18632/oncotarget.4173

M3 - Article

VL - 6

SP - 20946

EP - 20958

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 25

ER -

Lin HH, Lin HK, Lin IH, Chiou YW, Chen HW, Liu CY et al. Mechanical phenotype of cancer cells: Cell softening and loss of stiffness sensing. Oncotarget. 2015 Jan 1;6(25):20946-20958. https://doi.org/10.18632/oncotarget.4173