PMID- 38059420
OWN - NLM
STAT- MEDLINE
DCOM- 20240111
LR  - 20240325
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 137
IP  - 1
DP  - 2024 Jan 1
TI  - Inactivating negative regulators of cortical branched actin enhances persistence 
      of single cell migration.
LID - jcs261332 [pii]
LID - 10.1242/jcs.261332 [doi]
AB  - The Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched 
      actin, thereby powering membrane protrusions that mediate cell migration. Here, 
      using knockdown (KD) or knockout (KO), we combine the inactivation of the Arp2/3 
      inhibitory protein arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit 
      CYFIP2, all of which enhance the polymerization of cortical branched actin. 
      Inactivation of the three negative regulators of cortical branched actin 
      increases migration persistence of human breast MCF10A cells and of endodermal 
      cells in the zebrafish embryo, significantly more than any single or double 
      inactivation. In the triple KO cells, but not in triple KD cells, the 
      'super-migrator' phenotype was associated with a heterogenous downregulation of 
      vimentin (VIM) expression and a lack of coordination in collective behaviors, 
      such as wound healing and acinus morphogenesis. Re-expression of vimentin in 
      triple KO cells largely restored normal persistence of single cell migration, 
      suggesting that vimentin downregulation contributes to the maintenance of the 
      super-migrator phenotype in triple KO cells. Constant excessive production of 
      branched actin at the cell cortex thus commits cells into a motile state through 
      changes in gene expression.
CI  - (c) 2024. Published by The Company of Biologists Ltd.
FAU - Fokin, Artem I
AU  - Fokin AI
AUID- ORCID: 0000-0003-2205-8441
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
FAU - Boutillon, Arthur
AU  - Boutillon A
AUID- ORCID: 0000-0002-0968-6059
AD  - INSERM U1182, CNRS UMR7645, Ecole Polytechnique, Institut Polytechnique de Paris, 
      91120 Palaiseau, France.
FAU - James, John
AU  - James J
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
FAU - Courtois, Laura
AU  - Courtois L
AD  - Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 
      75005 Paris, France.
FAU - Vacher, Sophie
AU  - Vacher S
AUID- ORCID: 0000-0002-0042-6023
AD  - Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 
      75005 Paris, France.
FAU - Simanov, Gleb
AU  - Simanov G
AUID- ORCID: 0009-0004-0912-0946
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
FAU - Wang, Yanan
AU  - Wang Y
AUID- ORCID: 0000-0002-8050-3155
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
FAU - Polesskaya, Anna
AU  - Polesskaya A
AUID- ORCID: 0000-0002-7835-2335
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
FAU - Bieche, Ivan
AU  - Bieche I
AUID- ORCID: 0000-0002-2430-5429
AD  - Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 
      75005 Paris, France.
FAU - David, Nicolas B
AU  - David NB
AUID- ORCID: 0000-0003-1166-6732
AD  - INSERM U1182, CNRS UMR7645, Ecole Polytechnique, Institut Polytechnique de Paris, 
      91120 Palaiseau, France.
FAU - Gautreau, Alexis M
AU  - Gautreau AM
AUID- ORCID: 0000-0002-2369-4362
AD  - CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 
      Palaiseau, France.
LA  - eng
GR  - ANR-20-CE13-0016/Agence Nationale de la Recherche/
GR  - ARC PJA 2021 060003815/Fondation ARC pour la Recherche sur le Cancer/
GR  - INCA_11508/Institut National Du Cancer/
GR  - Fondation de l'Ecole Polytechnique/
GR  - Servier/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240110
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Vimentin)
RN  - 0 (Actin-Related Protein 2-3 Complex)
RN  - 0 (arpin protein, human)
RN  - 0 (Carrier Proteins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Actins/metabolism
MH  - Vimentin/genetics/metabolism
MH  - *Zebrafish/metabolism
MH  - Actin-Related Protein 2-3 Complex/genetics/metabolism
MH  - Cell Movement/physiology
MH  - Carrier Proteins/metabolism
OTO - NOTNLM
OT  - Arp2/3
OT  - Branched actin
OT  - Cell migration
OT  - Migration persistence
OT  - Vimentin
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2023/12/07 06:42
MHDA- 2024/01/11 07:43
CRDT- 2023/12/07 05:43
PHST- 2023/05/13 00:00 [received]
PHST- 2023/11/30 00:00 [accepted]
PHST- 2024/01/11 07:43 [medline]
PHST- 2023/12/07 06:42 [pubmed]
PHST- 2023/12/07 05:43 [entrez]
AID - 336525 [pii]
AID - 10.1242/jcs.261332 [doi]
PST - ppublish
SO  - J Cell Sci. 2024 Jan 1;137(1):jcs261332. doi: 10.1242/jcs.261332. Epub 2024 Jan 
      10.