RUNX2 and the PI3K/AKT axis reciprocal activation as a driving force for tumor progression

From the first reported role of the transcription factor RUNX2 in osteoblast and chondrocyte differentiation and migration to its involvement in promigratory/proinvasive behavior of breast, prostate, and thyroid cancer cells, osteosarcoma, or melanoma cells, RUNX2 currently emerges as a key player i...

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Bibliographic Details
Published in:Molecular cancer 2015-07, Vol.14 (1), p.137, Article 137
Main Authors: Cohen-Solal, Karine A, Boregowda, Rajeev K, Lasfar, Ahmed
Format: Article
Language:English
Subjects:
Analysis
Animals
Care and treatment
Cell Transformation, Neoplastic - metabolism
Core Binding Factor Alpha 1 Subunit - genetics
Core Binding Factor Alpha 1 Subunit - metabolism
Development and progression
Disease Progression
Gene Expression Regulation, Neoplastic
Humans
Melanoma
Metastasis
Mitogen-Activated Protein Kinases - metabolism
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Phosphatidylinositol 3-Kinases - metabolism
Protein Binding
Proto-Oncogene Proteins c-akt - metabolism
ras Proteins - metabolism
Review
Signal Transduction
Transforming Growth Factor beta - metabolism
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Summary:From the first reported role of the transcription factor RUNX2 in osteoblast and chondrocyte differentiation and migration to its involvement in promigratory/proinvasive behavior of breast, prostate, and thyroid cancer cells, osteosarcoma, or melanoma cells, RUNX2 currently emerges as a key player in metastasis. In this review, we address the interaction of RUNX2 with the PI3K/AKT signaling pathway, one of the critical axes controlling cancer growth and metastasis. AKT, either by directly phosphorylating/activating RUNX2 or phosphorylating/inactivating regulators of RUNX2 stability or activity, contributes to RUNX2 transcriptional activity. Reciprocally, the activation of the PI3K/AKT pathway by RUNX2 regulation of its different components has been described in non-transformed and transformed cells. This mutual activation in the context of cancer cells exhibiting constitutive AKT activation and high levels of RUNX2 might constitute a major driving force in tumor progression and aggressiveness.
ISSN:1476-4598
1476-4598
DOI:10.1186/s12943-015-0404-3