RhoA/ROCK signaling mediates plasticity of scirrhous gastric carcinoma motility

Matsuoka, Tasuku; Yashiro, Masakazu; Kato, Y.; Shinto, Osamu; Kashiwagi, Shinichiro; Hirakawa, Kosei

doi:10.1007/s10585-011-9396-6

Cited by 34 publications

(33 citation statements)

References 40 publications

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“…Conversely, Rho-kinase signaling can activate the Rac GAP ARH-GAP22 to suppress mesenchymal movement by inactivating Rac (25). The increased invasion of gastric cancer cells following treatment with ROCK1/2 inhibitors can be blocked with a Rac1 inhibitor (64), further demonstrating significant crosstalk between Rac1 and ROCK1/2 signaling. Overall, our results demonstrate the differential effects of Snail and Slug in pancreatic cancer and identify the interplay between Rho signaling and ␤1-integrin that functions to regulate scattering and migration of pancreatic cancer cells by Snail and Slug.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown that inhibiting Rho signaling using a dominant negative Rho mutant or ROCK1/2 inhibitors enhances migration of squamous cell cancer cells on collagen I (63). ROCK1/2 inhibitors also enhance invasion of gastric cancer cells through Matrigel (64). Rac1 and ROCK1/2 signaling have also been demonstrated to have an antagonistic effect on each other's cellular behavior (65).…”

Section: Discussionmentioning

confidence: 99%

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Interplay between β1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins

Shields

Krantz

Bentrem

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interplay between β1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins

Shields

Krantz

Bentrem

et al. 2012

Journal of Biological Chemistry

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“…However, it was also shown that Y-27632 increased the invasiveness of human glioma U87 and U251 cells [110] and also enhanced the invasion of human gastric carcinoma OCUM-2MD3 cells [111]. Time-lapse microscopy showed conversion of OCUM-2MD3 cells from a round to a more elongated morphology in the presence of Y-27632, and the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) was elevated, suggesting that inhibition of the RhoA/ROCK pathway undergoes AMT.…”

Section: Candidate Migrastatic Drugsmentioning

confidence: 98%

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

et al. 2017

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In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.

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“…The Rho family GTPase RhoA has been implicated in the regulation of cell contraction and retraction forces that are required for cell migration and invasion (20). In the current study, the activity of RhoA in glioblastoma cells in response to resveratrol was examined using a pull-down assay.…”

Section: Resveratrol Inhibits Activity and Expression Of Mmp-2 In Glimentioning

confidence: 99%

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

et al. 2015

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Abstract. Numerous studies have demonstrated that resveratrol has a potential use in cancer prevention and treatment. However, the effects of resveratrol on cancer cell motility and invasiveness remain unclear. The current study aimed to examine the effects of resveratrol on cell migration and invasion in human glioblastoma cells, and to explore the underlying molecular mechanisms. In wound-healing and Matrigel transwell assays, resveratrol was found to significantly inhibit the migration and invasion of U87MG, T98G and U251 glioblastoma cells in vitro. Results from western blot analysis and gelatin zymography revealed that resveratrol also suppressed the expression and activity of matrix metalloproteinase 2 (MMP-2; P<0.05), an important mediator of cell migration and invasion. Furthermore, using a pull-down assay, increased activation of RhoA was observed in glioblastoma cells treated with resveratrol vs. controls (P<0.05). Notably, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway by C3 transferase or Y-27362 was found to attenuate the resveratrol-induced reductions in cell migration and invasion (P<0.05), and also partially rescued the decreased expression and activity of MMP-2 induced by resveratrol (P<0.05). Taken together, the results suggest that resveratrol may inhibit glioblastoma cell motility and invasiveness via activating the RhoA/ROCK signaling pathway. IntroductionGlioblastoma is the most common and lethal intracranial malignant tumor with a yearly incidence of 3-4 per 100,000 (1). Despite the use of multimodal treatments, the prognosis of glioblastoma has been little improved, with a typical median survival time of only 12-15 months (2). Due to the diffuse infiltration of glioblastoma cells into the brain tissues, resection of the bulk tumor is typically followed by tumor reinitiation at the resection site or at another location in the brain. The highly aggressive and invasive properties of glioblastoma cells contribute significantly to the poor prognosis of cases involving this type of tumor (3). Therefore, it has been proposed that anti-invasion agents may play a crucial role in the treatment of glioblastoma (4).The invasion of malignant cancer cells is favored by degradation of the extracellular matrix (ECM), upregulation of proteolytic enzyme activity and an increase in tumor cell motility and invasive ability (5,6). Accumulating evidence has suggested that matrix metalloproteinases (MMPs) are capable of promoting tumor invasion and metastasis via degradation of the ECM (7), among which two gelatinases, MMP-2 and MMP-9, have attracted the most attention (8). Rho GTPases are a family of small GTP-binding proteins that serve as molecular switches in a wide variety of cellular signaling pathways, ultimately inducing changes in the organization of the actin cytoskeleton and regulating cell motility (9). It has been reported that RhoA activity is significantly reduced in astrocytic tumors (10-12), and increased RhoA activity in glioblastoma cells has been associated with impaired cell mi...

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RhoA/ROCK signaling mediates plasticity of scirrhous gastric carcinoma motility

Cited by 34 publications

References 40 publications

Interplay between β1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins

Interplay between β1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

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