Mechanical Stabilization of the Glandular Acinus by Linker of Nucleoskeleton and Cytoskeleton Complex.

3D culture LINC complex acinar development actomyosin contractility breast cancer fluctuations lumenal filling nuclear mechanics nucleus tissue mechanics

Journal

Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782

Informations de publication

Date de publication:
09 09 2019
Historique:
received: 24 01 2019
revised: 03 06 2019
accepted: 09 07 2019
pubmed: 14 8 2019
medline: 31 7 2020
entrez: 13 8 2019
Statut: ppublish

Résumé

The nucleoskeleton and cytoskeleton are important protein networks that govern cellular behavior and are connected together by the linker of nucleoskeleton and cytoskeleton (LINC) complex. Mutations in LINC complex components may be relevant to cancer, but how cell-level changes might translate into tissue-level malignancy is unclear. We used glandular epithelial cells in a three-dimensional culture model to investigate the effect of perturbations of the LINC complex on higher order cellular architecture. We show that inducible LINC complex disruption in human mammary epithelial MCF-10A cells and canine kidney epithelial MDCK II cells mechanically destabilizes the acinus. Lumenal collapse occurs because the acinus is unstable to increased mechanical tension that is caused by upregulation of Rho-kinase-dependent non-muscle myosin II motor activity. These findings provide a potential mechanistic explanation for how disruption of LINC complex may contribute to a loss of tissue structure in glandular epithelia.

Identifiants

pubmed: 31402305
pii: S0960-9822(19)30866-8
doi: 10.1016/j.cub.2019.07.021
pmc: PMC6736724
mid: NIHMS1537089
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2826-2839.e4

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM119617
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB014869
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103620
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA221320
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM099481
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103548
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016059
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

Qiao Zhang (Q)

Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.

Vani Narayanan (V)

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.

Keeley L Mui (KL)

Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Christopher S O'Bryan (CS)

Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL 32611, USA.

Ruthellen H Anderson (RH)

Enabling Technologies Group, Sanford Research, Sioux Falls, SD 57104, USA.

Birendra Kc (B)

Enabling Technologies Group, Sanford Research, Sioux Falls, SD 57104, USA.

Jolene I Cabe (JI)

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.

Kevin B Denis (KB)

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.

Susumu Antoku (S)

Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Kyle J Roux (KJ)

Enabling Technologies Group, Sanford Research, Sioux Falls, SD 57104, USA; Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA.

Richard B Dickinson (RB)

Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.

Thomas E Angelini (TE)

Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL 32611, USA.

Gregg G Gundersen (GG)

Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Daniel E Conway (DE)

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: dconway@vcu.edu.

Tanmay P Lele (TP)

Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA. Electronic address: tlele@che.ufl.edu.

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