ArticleOncogene2016
Role of Runx2 in IGF-1Rβ/Akt- and AMPK/Erk-dependent growth, survival and sensitivity towards metformin in breast cancer bone metastasis.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- The Role of Runx2 in Microtubule Dynamics and Its Effects on Osteoblast Migration.Cytoskeleton (Hoboken, N.J.) · 2026Article
- AMPK/mTORC2/AKT-473/RUNX2 signaling axis modulates epithelial-mesenchymal transition and bone tropism in breast cancer.Frontiers in oncology · 2026Article
- Farnesyltransferase inhibitors decrease matrix-vesicle-mediated mineralization in SaOS-2 cells.Molecular biology reports · 2025Article
- RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness.Journal of experimental & clinical cancer research : CR · 2025Article
- Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance.International journal of molecular sciences · 2025Review
- The Significant Role of RUNX2 Expression in Women with Metastatic Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- Article
- Itraconazole-Induced the Activation of Adenosine 5'-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling.Cell biochemistry and biophysics · 2022Article
- The Signaling Pathways Associated With Breast Cancer Bone Metastasis.Frontiers in oncology · 2022Review
- miR-23a-3p Regulates Runx2 to Inhibit the Proliferation and Metastasis of Oral Squamous Cell Carcinoma.Journal of oncology · 2022Article
- Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms.Cancers · 2021Review
- mClinical and translational medicine · 2021Article
- Review
- RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2021Article
- Use of signals of positive and negative selection to distinguish cancer genes and passenger genes.eLife · 2021Article
- Therapeutic effect of metformin in the treatment of endometrial cancer.Oncology letters · 2020Review
- Targeting the C-Terminal Domain Small Phosphatase 1.Life (Basel, Switzerland) · 2020Review
- Runx2 is required for activity of CD44American journal of translational research · 2020Article
- Synergistic effect of metformin and EGFR-TKI in the treatment of non-small cell lung cancer.Translational cancer research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying reprogramming of growth factor signaling and metabolic pathways during bone metastasis of breast cancer are not clear. The Runt-related transcription factor (Runx2) regulates cell signaling during mammary epithelial morphogenesis and promotes invasion; therefore, we investigated its role in cell growth and metabolic signaling in bone-seeking breast cancer cells. We performed systemic inoculation of control or Runx2 knockdown invasive MDA-MB-231 cells in NOD/SCID mice, and compared parental and bone-derived variants for phenotypic and molecular alterations. The Runx2 knockdown showed early (0-2 weeks) inhibition of metastatic spread but late (4-6 weeks) outgrowth, suggesting Runx2-dependent bi-phasic response and reprogramming of metastatic cells. The late-stage tumor outgrowth of bone-derived Runx2 knockdown cells was associated with increased insulin-like growth factor- 1Rβ (IGF-1Rβ) levels. Interestingly, glucose uptake and glycolysis were reduced in the bone-derived Runx2 knockdown cells that could be further reduced by extracellular-regulated protein kinase (Erk1/2) inhibition. Furthermore, the Runx2 knockdown cells displayed activation of AMP-activated protein kinase (AMPKα), the sensor of cellular metabolism. Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKα activation by PD184161 and metformin, respectively, despite increased IGF-1Rβ and AMPKα levels. Our results reveal that Runx2 promotes metastatic spread of mammary tumor cells. The growth of late-stage tumor cells can be targeted by Runx2 knockdown in combination with Mek-Erk1/2 inhibition and metformin treatment.
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Registered trials
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