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.G. Brunton; N. Barker; H. Clevers; O.J. Sansom; K.I. Anderson; V.M. Weaver; M.F. Olson

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

Translated title of the contribution: 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.G. Brunton, N. Barker, H. Clevers, O.J. Sansom, K.I. Anderson, V.M. Weaver, M.F. Olson

Research output: Contribution to journal › Article › Academic › peer-review

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.

Translated title of the contribution	Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth.
Original language	Undefined/Unknown
Pages (from-to)	776-91
Number of pages	16
Journal	Cancer Cell
Volume	19
Issue number	6
Publication status	Published - 2011

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Samuel, M. S., Lopez, J. I., McGhee, E. J., Croft, D. R., Strachan, D., Timpson, P., Munro, J., Schroder, E., Zhou, J., Brunton, V. G., 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), 776-91. http://www.ncbi.nlm.nih.gov/pubmed/21665151

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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.",

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.G. Brunton and N. Barker and H. Clevers and O.J. Sansom and K.I. Anderson and V.M. Weaver and M.F. Olson",

year = "2011",

language = "Undefined/Unknown",

volume = "19",

pages = "776--91",

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, VG, 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, no. 6, pp. 776-91. <http://www.ncbi.nlm.nih.gov/pubmed/21665151>

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.G.

AU - Barker, N.

AU - Clevers, H.

AU - Sansom, O.J.

AU - Anderson, K.I.

AU - Weaver, V.M.

AU - Olson, M.F.

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.

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.

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.

Abstract

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