ROCK1 and LIMK2 interact in spread but not blebbing cancer cells.
Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration.
Shea
Kerry F
KF
Randall Division of Cell & Molecular Biophysics, King's College London, London, United Kingdom.
Wells
Claire M
CM
Garner
Andrew P
AP
Jones
Gareth E
GE
D001943:Breast Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D022081:Cell Surface Extensions; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism*; D008853:Microscopy; D009362:Neoplasm Metastasis / Q000473:pathology; D010766:Phosphorylation; D054460:rho-Associated Kinases / Q000378:metabolism*
C102895:LIMK2 protein, human; D054461:Lim Kinases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases