RRC ID 37641
著者 Yamazaki D, Kurisu S, Takenawa T.
タイトル Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates.
ジャーナル Oncogene
Abstract The motility of cancer cells in 3D matrices is of two types: mesenchymal motility, in which the cells are elongated and amoeboid motility, in which the cells are round. Amoeboid motility is driven by an actomyosin-based contractile force, which is regulated by the Rho/ROCK pathway. However, the molecular mechanisms underlying the motility of elongated cells remain unknown. Here, we show that the motility of elongated cells is regulated by Rac signaling through the WAVE2/Arp2/3-dependent formation of elongated pseudopodia and cell-substrate adhesion in 3D substrates. The involvement of Rac signaling in cell motility was different in cell lines that displayed an elongated morphology in 3D substrates. In U87MG glioblastoma cells, most of which exhibit mesenchymal motility, inhibition of Rac signaling blocked the invasion of these cells in 3D substrates. In HT1080 fibrosarcoma cells, which display mixed cell motility involving both elongated and rounded cells, inhibition of Rac1 signaling not only blocked mesenchymal motility but also caused a mesenchymal-amoeboid transition. Additionally, Rac1 and RhoA signaling regulated the mesenchymal and amoeboid motility in these cells, respectively, and the inhibition of both pathways dramatically decreased cell invasion. Hence, we could conclude that Rac1 and RhoA signaling simultaneously regulate cell invasion in 3D matrices.
巻・号 28(13)
ページ 1570-83
公開日 2009-4-2
DOI 10.1038/onc.2009.2
PII onc20092
PMID 19234490
MeSH Cell Adhesion / genetics Cell Adhesion / physiology Cell Culture Techniques / methods Cell Movement / genetics Cell Movement / physiology* Cell Shape / genetics Cell Shape / physiology Collagen / pharmacology Gels / pharmacology Humans Mutant Proteins / metabolism Mutant Proteins / physiology Neoplasm Invasiveness Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology* Signal Transduction / genetics Signal Transduction / physiology Tumor Cells, Cultured rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism rac GTP-Binding Proteins / physiology* rac1 GTP-Binding Protein / genetics rac1 GTP-Binding Protein / metabolism rac1 GTP-Binding Protein / physiology rho GTP-Binding Proteins / genetics rho GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / physiology* rhoA GTP-Binding Protein / genetics rhoA GTP-Binding Protein / metabolism rhoA GTP-Binding Protein / physiology
IF 7.971
引用数 130
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY ONCOLOGY GENETICS & HEREDITY CELL BIOLOGY
リソース情報
ヒト・動物細胞