Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion
Open accessAbstract
The Rho subgroup of the Rho GTPases consisting of RhoA, RhoB and RhoC induces a specific type of actin cytoskeleton and carry out a variety of functions in the cell. mDia and ROCK are downstream effectors of Rho mediating Rho action on the actin cytoskeleton; mDia produces actin filaments by nucleation and polymerization and ROCK activate myosin to cross-link them for induction of actomyosin bundles and contractility. mDia is potentially linked to Rac activation and membrane ruffle formation through c-Src-induced phosphorylation of focal adhesion proteins, and ROCK antagonizes this mDia action. Thus, cell morphogenesis, adhesion, and motility can be determined by the balance between mDia and ROCK activities. Though they are not oncogenes by themselves, overexpression of RhoA and RhoC are often found in clinical cancers, and RhoC has been repeatedly identified as a gene associated with metastasis. The Rho-ROCK pathway is implicated in Ras-mediated transformation, the amoeboid movement of tumor cells in the three-dimensional matrix, and transmigration of tumor cells through the mesothelial monolayer. On the other hand, the Rho-mDia1 pathway is implicated in Src-mediated remodeling of focal adhesions and migration of tumor cells. There is also an indication that the Rho pathway other than ROCK is involved in Src-mediated induction of podosome and regulation of matrix metalloproteases. Thus, Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia.
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ROCK and mDia cooperate for actomyosin assembly and contractility, with mDia activation forming actin filaments and ROCK activating myosin to crosslink them.
“As mDia activation leads to the formation of actin filaments and ROCK activates myosin to crosslink them, ROCK and mDia cooperate for actomyosin assembly and contractility [122].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [122]
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- Authors
- Narumiya, S., Tanji, M., & Ishizaki, T.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Narumiya, Shuh
- ORCID
- Narumiya, Shuh
- Venue
- Cancer and Metastasis Reviews
- Published
- 2009-01-22
- Volume
- 28
- Issue
- 1-2
- Pages
- 65-76
- ISSN
- 0167-7659 (ISSN-L)
- 1573-7233
- OpenAlex
- W1984086927
- Cited by
- 530
- References
- 2
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 13 · 2023: 24 · 2022: 23 · 2021: 34 · 2020: 22 · 2019: 21 · 2018: 28 · 2017: 38 · 2016: 44 · 2015: 34 · 2014: 35 · 2013: 44 · 2012: 57
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cancer and Metastasis Reviews (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- Rho GTPases, RhoA, RhoB, RhoC, rocks, mDia1, actin cytoskeleton, cell motility, cell invasion, metastasis, malignant transformation, Ras signaling, Src kinase, focal adhesions, podosomes, matrix metalloproteinases, amoeboid migration, actomyosin contractility
- MeSH terms
- Formins, Animals, Cell Movement, Cell Transformation, Neoplastic, Humans, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, src-Family Kinases, Matrix Metalloproteinases, Adaptor Proteins, Signal Transducing, rho-Associated Kinases
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