TRAIL signaling promotes entosis in colorectal cancer.


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 07 10 2020
revised: 14 07 2021
accepted: 31 08 2021
entrez: 21 9 2021
pubmed: 22 9 2021
medline: 15 12 2021
Statut: ppublish

Résumé

Entosis is a form of nonphagocytic cell-in-cell (CIC) interaction where a living cell enters into another. Tumors show evidence of entosis; however, factors controlling entosis remain to be elucidated. Here, we find that besides inducing apoptosis, TRAIL signaling is a potent activator of entosis in colon cancer cells. Initiation of both apoptosis and entosis requires TRAIL receptors DR4 and DR5; however, induction of apoptosis and entosis diverges at caspase-8 as its structural presence is sufficient for induction of entosis but not apoptosis. Although apoptosis and entosis are morphologically and biochemically distinct, knockout of Bax and Bak, or inhibition of caspases, also inhibits entotic cell death and promotes survival and release of inner cells. Analysis of colorectal cancer tumors reveals a significant association between TRAIL signaling and CIC structures. Finally, the presence of CIC structures in the invasive front regions of colorectal tumors shows a strong correlation with adverse patient prognosis.

Identifiants

pubmed: 34546352
pii: 212649
doi: 10.1083/jcb.202010030
pmc: PMC8563286
pii:
doi:

Substances chimiques

Apoptosis Regulatory Proteins 0
Membrane Glycoproteins 0
Receptors, TNF-Related Apoptosis-Inducing Ligand 0
TNF-Related Apoptosis-Inducing Ligand 0
TNFSF10 protein, human 0
Tumor Necrosis Factor-alpha 0
Caspase 8 EC 3.4.22.-
Caspases EC 3.4.22.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Medical Research Council
ID : MR/S021205/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 24387
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T002824/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400302
Pays : United Kingdom
Organisme : Health Research Board
ID : 16/US/330
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 14/IA/2582
Pays : Ireland
Organisme : Wellcome Trust
ID : 110371/Z/15/Z
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021 Bozkurt et al.

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Auteurs

Emir Bozkurt (E)

Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Department of Genetics and Bioengineering, Faculty of Engineering, Izmir University of Economics, Balcova, Izmir, Turkey.

Heiko Düssmann (H)

Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Manuela Salvucci (M)

Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Brenton L Cavanagh (BL)

Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland, Dublin, Ireland.

Sandra Van Schaeybroeck (S)

Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.

Daniel B Longley (DB)

Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.

Seamus J Martin (SJ)

Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin, Ireland.

Jochen H M Prehn (JHM)

Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

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