Correlation between Rho-kinase pathway gene expressions and development and progression of glioblastoma multiforme

Erkutlu, İbrahim; Çiğiloğlu, Ahmet; Kalender, Mehmet; Alptekin, Mehmet; Demiryürek, Abdullah Tuncay; Suner, Ali; Ozkaya, Esma; Ulaşlı, Mustafa; Camcı, Celalettin

doi:10.1007/s13277-013-0655-9

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…Currently there is a lack of therapeutic agents targeting invasion and migration in GBM and there is a need for actionable targets involving these pathways. Having established that pCFL plays an integral role in GBM invasion, we explored how to target this pathway using small molecule inhibitors [ 12 , 13 , 26 ]. We tested LIMK1/2 and p-CFL inhibitors, BMS-5 and Cucurbitacin I.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway

et al. 2014

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Malignant gliomas are highly proliferative and invasive neoplasms where total surgical resection is often impossible and effective local radiation therapy difficult. Consequently, there is a need to develop a greater understanding of the molecular events driving invasion and to identify novel treatment targets. Using microarray analysis comparing normal brain samples and mesenchymal glioblastoma multiforme (GBM), we identified over 140 significant genes involved in cell migration and invasion. The cofilin (CFL) pathway, which disassembles actin filaments, was highly up-regulated compared to normal brain. Up-regulation of LIM domain kinase 1 and 2 (LIMK1/2), that phosphorylates and inactivates cofilin, was confirmed in an additional independent data set comparing normal brain to GBM. We identified and utilized two small molecule inhibitors BMS-5 and Cucurbitacin I directed against the cofilin regulating kinases, LIMK1 and LIMK2, to target this pathway. Significant decreases in cell viability were observed in glioma cells treated with BMS-5 and Cucurbitacin I, while no cytotoxic effects were seen in normal astrocytes that lack LIMK. BMS-5 and Cucurbitacin I promoted increased adhesion in GBM cells, and decreased migration and invasion. Collectively, these data suggest that use of LIMK inhibitors may provide a novel way to target the invasive machinery in GBM.

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Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway

et al. 2014

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“…The expression level of Cfl-2 has prognostic significance in primary leiomyosarcomas independent of the histopathological type of tumor, and its expression correlates with improved disease-specific survival [ 172 ]. Cfl-2 has also been identified in HMCs of non-muscle origin [ 173 , 174 , 175 , 176 ]. Cfl-2 has been overexpressed in aggressive breast cancer cell lines, and its expression has been correlated with tumor grade in primary breast cancer tissue [ 175 ].…”

Section: Members Of the Actin-depolymerizing Factor/cofilin Superfmentioning

confidence: 99%

Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells

Shishkin

Eremina

Pashintseva

et al. 2016

IJMS

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Identification of actin-depolymerizing factor homology (ADF-H) domains in the structures of several related proteins led first to the formation of the ADF/cofilin family, which then expanded to the ADF/cofilin superfamily. This superfamily includes the well-studied cofilin-1 (Cfl-1) and about a dozen different human proteins that interact directly or indirectly with the actin cytoskeleton, provide its remodeling, and alter cell motility. According to some data, Cfl-1 is contained in various human malignant cells (HMCs) and is involved in the formation of malignant properties, including invasiveness, metastatic potential, and resistance to chemotherapeutic drugs. The presence of other ADF/cofilin superfamily proteins in HMCs and their involvement in the regulation of cell motility were discovered with the use of various OMICS technologies. In our review, we discuss the results of the study of Cfl-1 and other ADF/cofilin superfamily proteins, which may be of interest for solving different problems of molecular oncology, as well as for the prospects of further investigations of these proteins in HMCs.

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“…In contrast, in pancreatic cancer, CFL2 showed lower expression compared with non-cancerous tissues [ 37 ]. The overexpression of CFL2 gene in glioblastoma multiforme contributes to increased therapeutic response [ 38 ]. These data suggested that the role of CFL2 varies in different kinds of cancers.…”

Section: Discussionmentioning

confidence: 99%

miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2

Bian

Guo

Qiao

et al. 2018

IJMS

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GDF15 is a downstream gene of S100A4. miR-3189 is embedded in the intron of GDF15—and coexpressed with it. miR-3189-3p functions to inhibit the proliferation and migration of glioblastoma cells. We speculated that S100A4 might regulate miR-3189-3p to affect its function in gastric cancer cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that miR-3189-3p expression was significantly downregulated in MGC803 cells after S100A4 knockdown. Overexpression of miR-3189-3p significantly inhibited the proliferation and migration of the cells. Moreover, miR-3189-3p mimics enhanced the effects of an S100A4 siRNA on the inhibition of cell proliferation and migration. Dual luciferase reporter assays, qRT-PCR, and Western blotting verified that CFL2 is a direct target of miR-3189-3p. CFL2 mediates the regulation of miR-3189-3p on the proliferation and migration of MGC803 cells. Data mining based on Kaplan–Meier plots showed that high CFL2 expression is associated with poor overall survival and first progression in gastric cancer. These data suggested that miR-3189-3p mimics enhanced the effects of the S100A4 siRNA on the inhibition of gastric cancer cell proliferation and migration by targeting CFL2. The findings suggested that when targeting S100A4 to treat gastric cancer, consideration and correction for counteracting factors should obtain a satisfactory effect.

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Correlation between Rho-kinase pathway gene expressions and development and progression of glioblastoma multiforme

Cited by 12 publications

References 34 publications

Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway

Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway

Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells

miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2

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