RUNX2 regulates genes involved in cell migration

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R-HSA-8941332
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Homo sapiens
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RUNX2 regulates expression of several genes implicated in cell migration during normal development and bone metastasis of breast cancer cells.
RUNX2 stimulates transcription of the ITGA5 gene, encoding Integrin alpha 5. Integrin alpha-5 promotes adhesion of breast cancer cells to the bone, thus facilitating formation of bone metastases (Li et al. 2016). ITGA5 is implicated in migration of human dental pulp stem cells (Xu et al. 2015). In zebrafish, Integrin alpha-5 coordinates cell migration during development of sensory organs (Bhat et al. 2011). During mouse retinal angiogenesis, Integrin alpha-5 regulates migration of endothelial cells (Stenzel et al. 2011).
The ITGBL1 gene encodes Integrin beta like protein 1, which is implicated in regulation of TGF-beta signaling and RUNX2-induced bone metastasis of breast cancer (Li et al. 2015).
RUNX2 mediated transcription of the MMP13 gene, encoding Colagenase 3 (Matrix metalloproteinase 13), is stimulated by AKT mediated phosphorylation of RUNX2 and is implicated in invasiveness of breast cancer cells (Pande et al. 2013). MMP13 is involved in migration of innate immune system cells in response to injury (Zhang et al. 2008) and in remodelling of skeletal tissues (Ortega et al. 2003).

Literature References
PubMed ID Title Journal Year
12814943 How proteases regulate bone morphogenesis

Ortega, N, Behonick, D, Stickens, D, Werb, Z

Ann. N. Y. Acad. Sci. 2003
22164214 Integrin-α5 coordinates assembly of posterior cranial placodes in zebrafish and enhances Fgf-dependent regulation of otic/epibranchial cells

Bhat, N, Riley, BB

PLoS ONE 2011
18641354 In vivo interstitial migration of primitive macrophages mediated by JNK-matrix metalloproteinase 13 signaling in response to acute injury

Zhang, Y, Bai, XT, Zhu, KY, Jin, Y, Deng, M, Le, HY, Fu, YF, Chen, Y, Zhu, J, Look, AT, Kanki, J, Chen, Z, Chen, SJ, Liu, TX

J. Immunol. 2008
21880786 Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis

Stenzel, D, Lundkvist, A, Sauvaget, D, Busse, M, Graupera, M, van der Flier, A, Wijelath, ES, Murray, J, Sobel, M, Costell, M, Takahashi, S, Fässler, R, Yamaguchi, Y, Gutmann, DH, Hynes, RO, Gerhardt, H

Development 2011
27317874 RUNX2 promotes breast cancer bone metastasis by increasing integrin α5-mediated colonization

Li, XQ, Lu, JT, Tan, CC, Wang, QS, Feng, YM

Cancer Lett. 2016
23389849 Oncogenic cooperation between PI3K/Akt signaling and transcription factor Runx2 promotes the invasive properties of metastatic breast cancer cells

Pande, S, Browne, G, Padmanabhan, S, Zaidi, SK, Lian, JB, van Wijnen, AJ, Stein, JL, Stein, GS

J. Cell. Physiol. 2013
26823759 Effect of ITGA5 down-regulation on the migration capacity of human dental pulp stem cells

Xu, S, Cui, L, Ma, D, Sun, W, Wu, B

Int J Clin Exp Pathol 2015
26060017 ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFβ Signaling Pathway

Li, XQ, Du, X, Li, DM, Kong, PZ, Sun, Y, Liu, PF, Wang, QS, Feng, YM

Cancer Res. 2015
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