Small GTP-binding Protein Rho Stimulates the Actomyosin System, Leading to Invasion of Tumor Cells

Yoshioka, Kiyoko; Matsumura, Fumio; Akedo, Hitoshi; Itoh, Kazuyuki

doi:10.1074/jbc.273.9.5146

Cited by 150 publications

(118 citation statements)

References 46 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…In control MDA-MB-231 cells, RhoA is predominantly associated with the cell membrane, suggesting that in these cancer cells the overexpression of RhoA facilitates its translocation from the cytosol to the cell membrane, as previously described (Yoshioka et al, 1998;Fritz et al, 1999). In contrast, after treatment with 1 mM ZOL for 18 h, RhoA was almost found in the cytosol fraction and the amount of this protein associated with the cell membrane was greatly reduced ( Figure 4A).…”

Section: Apoptosis and Inhibition Of Mda-mb-231 Cell Proliferation Resupporting

confidence: 73%

“…Since the small GTPase RhoA must be targeted to the plasma membrane for its activation (Yoshioka et al, 1998), we examined the effect of ZOL on the translocation of RhoA protein from the cytosol to the membrane fraction in MDA-MB-231 cells. In control MDA-MB-231 cells, RhoA is predominantly associated with the cell membrane, suggesting that in these cancer cells the overexpression of RhoA facilitates its translocation from the cytosol to the cell membrane, as previously described (Yoshioka et al, 1998;Fritz et al, 1999).…”

Section: Apoptosis and Inhibition Of Mda-mb-231 Cell Proliferation Rementioning

confidence: 99%

“…In colon carcinoma cells, expression of a dominant-negative RhoA resulted in the attenuation of cell invasion stimulated by the integrin a6b4 (O 'Connor et al, 2000). In the same way, cells transformed by the activated RhoA gene (del Peso et al, 1997) or cells expressing a constitutively active form of RhoA (Yoshioka et al, 1998) have greatly promoted invasive ability, contributing to the acquisition of a metastatic phenotype in vivo. Finally, we recently demonstrated that RhoA activation contributes to breast cancer cell aggressivity (Denoyelle et al, 2003).…”

mentioning

confidence: 99%

See 2 more Smart Citations

New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects

Denoyelle¹,

Li²,

Jp³

et al. 2003

Br J Cancer

146

110

View full text Add to dashboard Cite

Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate and its use in reducing osteoporosis and cancer-induced osteolysis is increasing. Recent findings indicated that ZOL has a direct effect on cancer cells. In this study, the effect of ZOL was examined on the aggressive MDA-MB-231 breast cancer cell line. ZOL induces an important inhibition of cell invasion at low concentrations (1 mM). This is not explained by modifications of proteases involved in cell invasiveness (matrix metalloproteinases and urokinase-type plasminogen activator), but by a disorganisation of actin cytoskeleton due to RhoA inhibition related to its defective prenylation as it was reversed by geranylgeraniol (GGOH) and mimicked by the Rho selective inhibitor C3 exoenzyme. In addition, ZOL inhibits the chemotactic effect induced by stromal cell-derived factor 1(SDF-1), a chemokine greatly involved in cancer metastasis to bone. This effect is related to both reduction of cell motility induced by RhoA inhibition and to a decreased expression of CXCR-4, the SDF-1 receptor. Finally, ZOL reduces Cox-2 expression and, consequently, the secretion of prostaglandins E2 (PGE2) in a RhoAindependent manner. This inhibition could contribute to bone protection in breast cancers because PGE2 stimulates osteoclastmediated bone resorption. In summary, new insights in the mechanism of ZOL action on aggressive breast cancer cells are demonstrated and could explain its beneficial action in both the reduction of osteolysis and prevention of metastasis.

show abstract

Section: Apoptosis and Inhibition Of Mda-mb-231 Cell Proliferation Resupporting

confidence: 73%

Section: Apoptosis and Inhibition Of Mda-mb-231 Cell Proliferation Rementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects

Denoyelle¹,

Li²,

Jp³

et al. 2003

Br J Cancer

146

110

View full text Add to dashboard Cite

show abstract

“…6 Increased MRLC phosphorylation has been demonstrated to parallel an increase in motility and/or invasiveness of cells overexpressing upstream regulators of MLCK and MRLC, whereas inhibition of MRLC phosphorylation showed reversed effects. [7][8][9][10] The MLL cell, a rat prostatic adenocarcinoma, is highly metastatic in vivo, correlating with its highly invasive behaviour in vitro as demonstrated by the in vitro invasion assay. 11 Here, we show that in vitro invasion of MLL cells was severely inhibited by treatment with the MLCK inhibitors, ML-7 and ML-9, while the ability to survive and proliferate was minimally affected.…”

Section: Metastatic Cancer Cell Invasionmentioning

confidence: 99%

Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain

Tohtong

Phattarasakul

Jiraviriyakul

et al. 2003

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

The role of myosin phosphorylation by myosin light chain kinase (MLCK) in regulating the invasiveness of metastatic cancer cells was investigated using the Dunning rat prostatic adenocarcinoma cell line, Mat Ly Lu, and in vitro invasion assay. Treatment with MLCK inhibitors resulted in marked reduction of invasiveness, which was principally due to impaired cellular motility, whereas the ability to survive and proliferate, to adhere to matrix, and to secrete gelatinases were minimally affected.

show abstract

“…The small GTPase Rho and its target Rho-associated protein kinases (Rho kinase, p160ROCK) [9,18,19] control cell adhesion [10] and motility [35] through reorganization of the actin cytoskeleton and regulation of actomyosin contractility [3] in a number of cellular processes, including vascular contraction [31], tumor invasion [12], penile erection [2], and apoptosis [4]. Further, several lines of evidence indicated that Rho-ROCK signaling also has been involved in cellular transformation.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Yoshikawa

Yoshioka

Nakase

et al. 2009

Clin Orthop Relat Res

Self Cite

View full text Add to dashboard Cite

The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation.

show abstract

Small GTP-binding Protein Rho Stimulates the Actomyosin System, Leading to Invasion of Tumor Cells

Cited by 150 publications

References 46 publications

New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects

New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects

Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Contact Info

Product

Resources

About