GSBS Student Publications

Title

Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone

UMMS Affiliation

Graduate School of Biomedical Sciences; Graduate School of Biomedical Sciences; Department of Cell Biology

Date

12-14-2006

Document Type

Article

Medical Subject Headings

Animals; Bone and Bones; Core Binding Factor Alpha 1 Subunit; *Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Neoplasms; Osteolysis

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The three mammalian Runt homology domain transcription factors (Runx1, Runx2, Runx3) support biological control by functioning as master regulatory genes for the differentiation of distinct tissues. Runx proteins also function as cell context-dependent tumor suppressors or oncogenes. Abnormalities in Runx mediated gene expression are linked to cell transformation and tumor progression. Runx2 is expressed in mesenchymal linage cells committed to the osteoblast phenotype and is essential for bone formation. This skeletal transcription factor is aberrantly expressed at high levels in breast and prostate tumors and cells that aggressively metastasize to the bone environment. In cancer cells, Runx2 activates expression of bone matrix and adhesion proteins, matrix metalloproteinases and angiogenic factors that have long been associated with metastasis. In addition, Runx2 mediates the responses of cells to signaling pathways hyperactive in tumors, including BMP/TGFbeta and other growth factor signals. Runx2 forms co-regulatory complexes with Smads and other co-activator and co-repressor proteins that are organized in subnuclear domains to regulate gene transcription. These activities of Runx2 contribute to tumor growth in bone and the accompanying osteolytic disease, established by interfering with Runx2 functions in metastatic breast cancer cells. Inhibition of Runx2 in MDA-MB-231 cells transplanted to bone decreased tumorigenesis and prevented osteolysis. This review evaluates evidence that Runx2 regulates early metastatic events in breast and prostate cancers, tumor growth, and osteolytic bone disease. Consideration is given to the potential for inhibition of this transcription factor as a therapeutic strategy upstream of the regulatory events contributing to the complexity of metastasis to bone.

Rights and Permissions

Citation: Cancer Metastasis Rev. 2006 Dec;25(4):589-600. Link to article on publisher's site

DOI of Published Version

10.1007/s10555-006-9032-0

Related Resources

Link to article in PubMed

Journal Title

Cancer metastasis reviews

PubMed ID

17165130