Runx Protein Signaling in Human Cancers

Anglin, Ian E.; Passaniti, Antonio

doi:10.1007/1-4020-7847-1_10

Cited by 19 publications

(18 citation statements)

References 145 publications

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“…Therefore, Runx family proteins regulate angiogenesis differently, in that RUNX1 and RUNX3 inhibit angiogenesis and Runx2 stimulates angiogenesis. It is interesting that the hypothetical functions of RUNX1 and RUNX3 are as tumor suppressors and that Runx2 functions as an oncogenic protein (41). Therefore, in FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Lee¹,

Che

Jeong

et al. 2012

Journal of Biological Chemistry

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Background: Runt-related transcription factor 2 (Runx2) is a key factor in bone development. Hypoxia-inducible factor-1␣ (HIF-1␣) is the primary regulator of blood vessel formation. Results: Runx2 bound and activated HIF-1␣ by competing with von Hippel-Lindau protein (pVHL), protecting HIF-1␣ from degradation. Conclusion: Runx2 stabilizes HIF-1␣ during endochondral bone formation. Significance: Runx2/HIF-1␣ stimulate the invasion of blood vessels in hypertrophic zones.

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Section: Discussionmentioning

confidence: 99%

Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Lee¹,

Che

Jeong

et al. 2012

Journal of Biological Chemistry

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“…Bone morphogenetic proteins (BMP), trigger a Smad-signaling cascade that is linked to reduced cell proliferation and cellular growth kinetics of glioblastomas [10, 11]. The Runt-related transcription factors (RUNX), RUNX1 , RUNX2 , and RUNX3 [12] are involved in signaling cascades mediated by TGF-β and BMP [13–16]. All three of the RUNX genes have been shown to bind Smads [17–19].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in the TGFβ-signaling pathway influence expression of miRNAs in colon and rectal normal mucosa and tumor tissue

et al. 2017

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The TGF-β signaling pathway is involved in regulation of cell growth, angiogenesis, and metastasis. We test the hypothesis that genetic variation in the TGF-β signaling pathway alters miRNA expression.We use data from 1188 colorectal cancer cases to evaluate associations between 80 SNPs in 21 genes.Seven variants eIF4E rs12498533, NFκB1 rs230510, TGFB1 rs4803455, TGFBR1 rs1571590 and rs6478974, SMAD3 rs3743343, and RUNX1 rs8134179 were associated with expression level of miRNAs in normal colorectal mucosa. RUNX2 rs12333172 and BMPR1B rs13134042 were associated with miRNAs in normal colon mucosa; eIF4EBP3 rs250425, SMAD3 rs12904944, SMAD7 rs3736242, and PTEN rs532678 were associated with miRNA expression in normal rectal mucosa. Evaluation of the differential expression between carcinoma and normal mucosa showed that SMAD3 rs12708491 and rs2414937, NFκB1 rs230510 and rs3821958, and RUNX3 rs6672420 were associated with several miRNAs for colorectal carcinoma. Evaluation of site-specific differential miRNA expression showed that BMPR1B rs2120834, BMPR2 rs2228545, and eIF4EBP3 rs250425 were associated with differential miRNA expression in colon tissue and SMAD3 rs12901071, rs1498506, and rs2414937, BMPR2 rs2228545, and RUNX2 rs2819854, altered differential miRNA expression in rectal tissue.These data support the importance of the TGF-β signaling pathway to the carcinogenic process, possibly through their influence on miRNA expression levels.

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“…It regulates the promoter of the TGF␤ type I receptor and interacts with Smad signaling intermediates to control both cell proliferation and differentiation in several developmental systems (33,34). The RUNX2 protein interacts with coactivators and corepressors through specific domains to regulate transcription of target genes (2,35). RUNX2 may promote cell proliferation by interacting with histone deacetylase 6 at the carboxyl-terminal to repress the p21 Cip1/Waf1 promoter in mesenchymal fibroblast and osteoblast cells (36).…”

mentioning

confidence: 99%

Cell Cycle-dependent Phosphorylation of the RUNX2 Transcription Factor by cdc2 Regulates Endothelial Cell Proliferation

Qiao

Shapiro

Fosbrink

et al. 2006

Journal of Biological Chemistry

105

109

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RUNX2 is a member of the runt family of DNA-binding transcription factors. RUNX2 mediates endothelial cell migration and invasion during tumor angiogenesis and is expressed in metastatic breast and prostate tumors. Our published studies showed that RUNX2 DNA-binding activity is low during growth arrest, but elevated in proliferating endothelial cells. To investigate its role in cell proliferation and cell cycle regulation, RUNX2 was depleted in human bone marrow endothelial cells using RNA interference. Specific RUNX2 depletion inhibited DNA-binding activity as measured by electrophoretic mobility shift assay resulting in inhibition of cell proliferation. Cells were synchronized at the G 1 /S boundary with excess thymidine or in mitosis (M phase) with nocodazole. Endogenous or ectopic RUNX2 activity was maximal at late G 2 and during M phase. Inhibition of RUNX2 expression by RNA interference delayed entry into and exit out of the G 2 /M phases of the cell cycle. RUNX2 was coimmunoprecipitated with cyclin B1 in mitotic cells, which further supported a role for RUNX2 in cell cycle progression. Moreover, in vitro kinase assays using recombinant cdc2 kinase showed that RUNX2 was phosphorylated at Ser 451 . The cdc2 inhibitor roscovitine dose dependently inhibited in vivo RUNX2 DNAbinding activity during mitosis and the RUNX2 mutant S451A exhibited lower DNA-binding activity and reduced stimulation of anchorage-independent growth relative to wild type RUNX2. These results suggest for the first time that RUNX2 phosphorylation by cdc2 may facilitate cell cycle progression possibly through regulation of G 2 and M phases, thus promoting endothelial cell proliferation required for tumor angiogenesis.The RUNX gene family of transcriptional regulators is the mammalian homologue of the Drosophila transcription factor runt. The three RUNX factors contain an evolutionarily conserved 128-amino acid runt domain, which is responsible for DNA binding and heterodimerization with the cofactor CBF␤ (1-3). RUNX factors are essential regulators of hematopoietic (4 -6), osteogenic (7-10), and gastric development (11-13). RUNX2 promotes preosteoblast growth and osteoblast lineage commitment (14 -16). Mice nullizygous for RUNX2 lack bone matrix gene expression and exhibit no bone formation, whereas heterozygous mice display skeletal abnormalities similar to cleidocranial dysplasia in humans (17)(18)(19)(20). Increasing evidence suggests that RUNX2 exhibits oncogenic potential in a wide variety of cells (21). Expression of RUNX2 is higher in H-Ras-transformed NIH3T3 fibroblasts compared with normal cells (22) and, after retroviral integration in T-cells, RUNX2 expression cooperates with c-Myc to stimulate cell growth (23). Forced expression of Runx2 in transgenic mice was found to interfere with T-cell development and to predispose mice to lymphoma (23). Endogenous RUNX2 is expressed in malignant breast cancer cells and prostate tumors, regulates bone sialoprotein expression, and promotes osteolytic lesions in breast cancer metastases (24...

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Runx Protein Signaling in Human Cancers

Cited by 19 publications

References 145 publications

Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Genetic variants in the TGFβ-signaling pathway influence expression of miRNAs in colon and rectal normal mucosa and tumor tissue

Cell Cycle-dependent Phosphorylation of the RUNX2 Transcription Factor by cdc2 Regulates Endothelial Cell Proliferation

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