ArticleJournal of cellular physiology2013
Oncogenic cooperation between PI3K/Akt signaling and transcription factor Runx2 promotes the invasive properties of metastatic breast cancer cells.
Article in Journal of cellular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
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- Runt-related transcription factors in human carcinogenesis: a friend or foe?Journal of cancer research and clinical oncology · 2023Review
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- Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2.International journal of molecular sciences · 2022Article
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- SIRT6 protects vascular smooth muscle cells from osteogenic transdifferentiation via Runx2 in chronic kidney disease.The Journal of clinical investigation · 2022Article
- Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases.Frontiers in immunology · 2021Review
- Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Specific Akt Family Members Impair Stress-Mediated Transactivation of Viral Promoters and Enhance Neuronal Differentiation: Important Functions for Maintaining Latency.Journal of virology · 2020Article
- Delayed tooth movement in Runx2Bone reports · 2020Article
- Post-Translational Regulations of Transcriptional Activity of RUNX2.Molecules and cells · 2020Review
- The Thyroid Hormone Receptor-RUNX2 Axis: A Novel Tumor Suppressive Pathway in Breast Cancer.Hormones & cancer · 2020Article
- RUNX2 overexpression and PTEN haploinsufficiency cooperate to promote CXCR7 expression and cellular trafficking, AKT hyperactivation and prostate tumorigenesis.Theranostics · 2019Article
- Identification ofHereditas · 2019Article
- miR-182 and miR-135b Mediate the Tumorigenesis and Invasiveness of Colorectal Cancer Cells via Targeting ST6GALNAC2 and PI3K/AKT Pathway.Digestive diseases and sciences · 2017Article
- Novel Mutation of theMolecular syndromology · 2017Article
- Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The serine/threonine kinase Akt/PKB promotes cancer cell growth and invasion through several downstream targets. Identification of novel substrates may provide new avenues for therapeutic intervention. Our study shows that Akt phosphorylates the cancer-related transcription factor Runx2 resulting in stimulated DNA binding of the purified recombinant protein in vitro. Pharmacological inhibition of the PI3K/Akt pathway in breast cancer cells reduces DNA-binding activity of Runx2 with concomitant reduction in the expression of metastasis-related Runx2 target genes. Akt phosphorylates Runx2 at three critical residues within the runt DNA-binding domain to enhance its in vivo genomic interactions with a target gene promoter, MMP13. Mutation of these three phosphorylation sites reduces Runx2 DNA-binding activity. However, Akt signaling does not appear to interefere with CBFβ-Runx2 interactions. Consequently, expression of multiple metastasis-related genes is decreased and Runx2-mediated cell invasion is supressed. Thus, our work identifies Runx2 as a novel and important downstream mediator of the PI3K/Akt pathway that is linked to metastatic properties of breast cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.