title: LIM-kinase is critical for the mesenchymal-to-amoeboid cell morphological transition in 3D matrices.
abstract: Tumor cells can migrate in 3D matrices in either a mesenchymal-like or amoeboid mode. HT1080 fibrosarcoma cells cultured in 3D collagen gels change their morphology from mesenchymal-like (elongated) to amoeboid (round) following protease inhibitor (PI) treatment or active Rho or ROCK expression. In this study, we examined the role of LIM-kinase 1 (LIMK1) in the PI- or Rho/ROCK-induced cell morphological change. We showed that LIMK1 was activated after PI treatment of HT1080 cells in 3D collagen gels and this activation was blocked by a ROCK inhibitor. While overexpression of LIMK1 induced cell rounding, knockdown of LIMK1 or the expression of kinase-inactive LIMK1 suppressed PI- or Rho/ROCK-induced cell rounding. These results suggest that LIMK1 plays an essential role in the PI- or Rho/ROCK-induced mesenchymal-to-amoeboid cell morphological transition of HT1080 cells cultured in 3D collagen gels. Furthermore, LIMK1 knockdown suppressed the invasive activity of HT1080 cells in collagen gels with or without PIs, indicating that LIMK1 mediates both the mesenchymal and amoeboid modes of invasion of HT1080 cells.
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mishima
authors.forename: Moyu
authors.initials: M
authors.lastname: Naotsuka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Horita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ohashi
authors.forename: Kensaku
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D005782:Gels / Q000737:chemistry / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D005782:Gels; D003094:Collagen; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins