Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth

M.S. Samuel; J.I. Lopez; E.J. McGhee; D.R. Croft; D. Strachan; P. Timpson; J. Munro; E. Schroder; J. Zhou; V. Brunton; N. Barker; H. Clevers; O.J. Sansom; K.I. Anderson; V.M. Weaver; M.F. Olson

doi:10.1016/j.ccr.2011.05.008

Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth

M.S. Samuel, J.I. Lopez, E.J. McGhee, D.R. Croft, D. Strachan, P. Timpson, J. Munro, E. Schroder, J. Zhou, V. Brunton, N. Barker, H. Clevers, O.J. Sansom, K.I. Anderson, V.M. Weaver, M.F. Olson

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

441 Citaten (Scopus)

Samenvatting

Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. beta-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. [KEYWORDS: Actomyosin/ physiology, Animals, Biomechanics, Cell Proliferation, Cells, Cultured, Epidermis/ pathology, Humans, Hyperplasia, Mice, Papilloma/etiology, Signal Transduction, Skin Neoplasms/ etiology, beta Catenin/ physiology, rho-Associated Kinases/analysis/genetics/physiology]

Originele taal-2	Engels
Pagina's (van-tot)	776-791
Tijdschrift	Cancer Cell
Volume	19
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.ccr.2011.05.008
Status	Gepubliceerd - 2011

Toegang tot document

10.1016/j.ccr.2011.05.008Licentie: Other

Citeer dit

Samuel, M. S., Lopez, J. I., McGhee, E. J., Croft, D. R., Strachan, D., Timpson, P., Munro, J., Schroder, E., Zhou, J., Brunton, V., Barker, N., Clevers, H., Sansom, O. J., Anderson, K. I., Weaver, V. M., & Olson, M. F. (2011). Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell, 19(6), 776-791. https://doi.org/10.1016/j.ccr.2011.05.008

@article{52856fda38ac4a15832e12ccd7a0d2eb,

title = "Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth",

abstract = "Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. beta-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. [KEYWORDS: Actomyosin/ physiology, Animals, Biomechanics, Cell Proliferation, Cells, Cultured, Epidermis/ pathology, Humans, Hyperplasia, Mice, Papilloma/etiology, Signal Transduction, Skin Neoplasms/ etiology, beta Catenin/ physiology, rho-Associated Kinases/analysis/genetics/physiology]",

author = "M.S. Samuel and J.I. Lopez and E.J. McGhee and D.R. Croft and D. Strachan and P. Timpson and J. Munro and E. Schroder and J. Zhou and V. Brunton and N. Barker and H. Clevers and O.J. Sansom and K.I. Anderson and V.M. Weaver and M.F. Olson",

note = "Reporting year: 2011 Metis note: 3115541;",

year = "2011",

doi = "10.1016/j.ccr.2011.05.008",

language = "English",

volume = "19",

pages = "776--791",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

Samuel, MS, Lopez, JI, McGhee, EJ, Croft, DR, Strachan, D, Timpson, P, Munro, J, Schroder, E, Zhou, J, Brunton, V, Barker, N, Clevers, H, Sansom, OJ, Anderson, KI, Weaver, VM & Olson, MF 2011, 'Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth', Cancer Cell, vol. 19, nr. 6, blz. 776-791. https://doi.org/10.1016/j.ccr.2011.05.008

Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth. / Samuel, M.S.; Lopez, J.I.; McGhee, E.J. et al.
In: Cancer Cell, Vol. 19, Nr. 6, 2011, blz. 776-791.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth

AU - Samuel, M.S.

AU - Lopez, J.I.

AU - McGhee, E.J.

AU - Croft, D.R.

AU - Strachan, D.

AU - Timpson, P.

AU - Munro, J.

AU - Schroder, E.

AU - Zhou, J.

AU - Brunton, V.

AU - Barker, N.

AU - Clevers, H.

AU - Sansom, O.J.

AU - Anderson, K.I.

AU - Weaver, V.M.

AU - Olson, M.F.

N1 - Reporting year: 2011 Metis note: 3115541;

PY - 2011

Y1 - 2011

N2 - Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. beta-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. [KEYWORDS: Actomyosin/ physiology, Animals, Biomechanics, Cell Proliferation, Cells, Cultured, Epidermis/ pathology, Humans, Hyperplasia, Mice, Papilloma/etiology, Signal Transduction, Skin Neoplasms/ etiology, beta Catenin/ physiology, rho-Associated Kinases/analysis/genetics/physiology]

AB - Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. beta-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. [KEYWORDS: Actomyosin/ physiology, Animals, Biomechanics, Cell Proliferation, Cells, Cultured, Epidermis/ pathology, Humans, Hyperplasia, Mice, Papilloma/etiology, Signal Transduction, Skin Neoplasms/ etiology, beta Catenin/ physiology, rho-Associated Kinases/analysis/genetics/physiology]

U2 - 10.1016/j.ccr.2011.05.008

DO - 10.1016/j.ccr.2011.05.008

M3 - Article

SN - 1535-6108

VL - 19

SP - 776

EP - 791

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth

Samenvatting

Toegang tot document

Vingerafdruk

Citeer dit