Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity

Zhang, Xuejiao; Cheng, Li; Gao, Huiling; Nabeka, Hiroaki; Shimokawa, Tetsuya; Wakisaka, Hiroyuki; Matsuda, Seiji; Kobayashi, Naoto

doi:10.2478/s11658-011-0006-z

Cited by 22 publications

(20 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40,41 Both increase and decrease in the migration rate have been reported after ROCK inhibition, depending on the cell type. 35,[42][43][44][45] However, although the two isoforms ROCK1 and 2 were generally assumed to have the same functions, whenever a distinction between the two ROCKs has been drawn, ROCK2 depletion has been reported as enhancing microfilament bundle assembly into stress fibre and focal adhesion formation, whereas ROCK1 depleted cells show an opposite phenotype. [46][47][48] We observed a specific downregulation of ROCK2 in CD99wt-expressing cells, and modulation of it was functionally associated with modified adhesive and migratory behaviour by osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 97%

CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity

et al. 2013

View full text Add to dashboard Cite

CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions. In osteosarcoma, CD99 is expressed at low levels and functions as a tumour suppressor. The full-length protein (CD99wt) and the short-form harbouring a deletion in the intracytoplasmic domain (CD99sh) have been associated with distinct functional outcomes with respect to tumour malignancy. In this study, we especially evaluated modulation of cell-cell contacts, reorganisation of the actin cytoskeleton and modulation of signalling pathways by comparing osteosarcoma cells characterised by different metastasis capabilities and CD99 expression, to identify molecular mechanisms responsible for metastasis. Our data indicate that forced expression of CD99wt induces recruitment of N-cadherin and β-catenin to adherens junctions. In addition, transfection of CD99wt inhibits the expression of several molecules crucial to the remodelling of the actin cytoskeleton, such as ACTR2, ARPC1A, Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) as well as ezrin, an ezrin/radixin/moesin family member that has been clearly associated with tumour progression and metastatic spread in osteosarcoma. Functional studies point to ROCK2 as a crucial intracellular mediator regulating osteosarcoma migration. By maintaining c-Src in an inactive conformation, CD99wt inhibits ROCK2 signalling and this leads to ezrin decrease at cell membrane while N-cadherin and β-catenin translocate to the plasma membrane and function as main molecular bridges for actin cytoskeleton. Taken together, we propose that the re-expression of CD99wt, which is generally present in osteoblasts but lost in osteosarcoma, through inhibition of c-Src and ROCK2 activity, manages to increase contact strength and reactivate stop-migration signals that counteract the otherwise dominant promigratory action of ezrin in osteosarcoma cells.

show abstract

Section: Discussionmentioning

confidence: 97%

CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Therefore, the RhoA/ROCK/MLC signaling pathway negative regulates the migration of 786-0 cells, which is in accordance with our hypothesis. As ROCK-related signaling antagonizes the activity of Rac in osteoblasts, fibroblasts and rat basophilic leukemia cells (42)(43)(44), the involved mechanism might be through activation of Rac. Activated Rac induces the formation of actin-based sheet-like membrane projections from the cell periphery named lamellipodia (45), which plays a key role in the stimulation of cell migration (46).…”

Section: Discussionmentioning

confidence: 99%

Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway

Cheng

Castillo

Welty

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Honokiol, a biologically active compound isolated from Magnolia bark, has been shown to possess promising anticancer effect through induction of apoptosis. However, there is a relative lack of information regarding its anti-metastatic activity. Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney and is known for high risk of metastasis. Clinically, therapeutic methods for metastatic RCC cases are limited and efforts to exploit new treatments are still ongoing. The results of our current investigation first revealed that honokiol suppressed the proliferation of different human RCCs without affecting cell viability. In addition, honokiol inhibited migration of highly metastatic RCC 786-0 cells and stimulated the activity of small GTPase, RhoA. Furthermore, phosphorylated myosin light chain (MLC) and excessive formation of actin stress fibers were identified in 786-0 cells treated with honokiol. Interestingly, the pharmacological Rho-associated protein kinase (ROCK) inhibitor Y-27632 attenuated contraction of actin stress fibers induced by honokiol and abrogated honokiol-mediated inhibition of cell migration. Together these important findings suggest that honokiol suppresses the migration of highly metastatic RCC through activation of RhoA/ROCK/MLC signaling and warrants attention in the treatment of RCC metastasis as a novel therapeutic approach.

show abstract

“…Among the MAP kinase superfamily, three MAP kinases—p44/p42 MAP kinase, p38 MAP kinase and SAPK/JNK—are recognized to function as central intracellular elements to transduce the diverse messages [27]. In contrast, Rho-kinase reportedly acts as a negative regulator in migration of osteoblasts [38]. In addition, accumulating evidence suggests that p70 S6 kinase is implicated in the migration of several cancer cells [29].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Inhibits the Epidermal Growth Factor-Induced Migration of Osteoblasts: the Suppression of SAPK/JNK and Akt

Kawabata

Tokuda

Fujita

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. Methods: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting. Results: The EGF-induced migration was suppressed by PD98059, an inhibitor of MEK1/2, as well as SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of SAPK/JNK, and deguelin, an inhibitor of Akt. In contrast, rapamycin, an inhibitor of upstream kinase of p70 S6 kinase, and fasudil, an inhibitor of Rho-kinase, hardly affected the migration. Resveratrol significantly reduced the EGF-induced migration in a dose-dependent manner. SRT1720, an SIRT1 activator, suppressed the migration by EGF. In addition, resveratrol markedly attenuated the EGF-induced phosphorylation of SAPK/JNK and Akt without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. The phosphorylation of SAPK/JNK and Akt induced by EGF was down-regulated by SRT1720. Conclusion: Our results strongly suggest that resveratrol reduces the EGF-stimulated migration of osteoblasts via suppression of SAPK and Akt, and that the inhibitory effect of resveratrol is mediated in part via SIRT1.

show abstract

Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity

Cited by 22 publications

References 37 publications

CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity

CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity

Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway

Resveratrol Inhibits the Epidermal Growth Factor-Induced Migration of Osteoblasts: the Suppression of SAPK/JNK and Akt

Contact Info

Product

Resources

About