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

J. Pratap, J. B. Lian, A. Javed, G. L. Barnes, Andre J van Wijnen, J. L. Stein, G. S. Stein

Research output: Contribution to journalArticle

175 Citations (Scopus)

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/TGFβ 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.

Original languageEnglish (US)
Pages (from-to)589-600
Number of pages12
JournalCancer and Metastasis Reviews
Volume25
Issue number4
DOIs
StatePublished - Dec 2006
Externally publishedYes

Fingerprint

Cell Communication
Bone and Bones
Neoplasms
Transcription Factors
Breast Neoplasms
Core Binding Factor alpha Subunits
Neoplasm Metastasis
Co-Repressor Proteins
Osteolysis
Bone Matrix
Angiogenesis Inducing Agents
Bone Diseases
Bone Development
Regulator Genes
Osteoblasts
Matrix Metalloproteinases
Oncogenes
Osteogenesis
Prostate
Prostatic Neoplasms

Keywords

  • Bone metastasis
  • Breast cancer
  • Osteolysis
  • Osteolytic disease
  • Prostate cancer
  • Smads

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pratap, J., Lian, J. B., Javed, A., Barnes, G. L., van Wijnen, A. J., Stein, J. L., & Stein, G. S. (2006). Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer and Metastasis Reviews, 25(4), 589-600. https://doi.org/10.1007/s10555-006-9032-0

Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. / Pratap, J.; Lian, J. B.; Javed, A.; Barnes, G. L.; van Wijnen, Andre J; Stein, J. L.; Stein, G. S.

In: Cancer and Metastasis Reviews, Vol. 25, No. 4, 12.2006, p. 589-600.

Research output: Contribution to journalArticle

Pratap, J, Lian, JB, Javed, A, Barnes, GL, van Wijnen, AJ, Stein, JL & Stein, GS 2006, 'Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone', Cancer and Metastasis Reviews, vol. 25, no. 4, pp. 589-600. https://doi.org/10.1007/s10555-006-9032-0
Pratap, J. ; Lian, J. B. ; Javed, A. ; Barnes, G. L. ; van Wijnen, Andre J ; Stein, J. L. ; Stein, G. S. / Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. In: Cancer and Metastasis Reviews. 2006 ; Vol. 25, No. 4. pp. 589-600.
@article{314e4b745b254512b6dc93d8045ce461,
title = "Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone",
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/TGFβ 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.",
keywords = "Bone metastasis, Breast cancer, Osteolysis, Osteolytic disease, Prostate cancer, Smads",
author = "J. Pratap and Lian, {J. B.} and A. Javed and Barnes, {G. L.} and {van Wijnen}, {Andre J} and Stein, {J. L.} and Stein, {G. S.}",
year = "2006",
month = "12",
doi = "10.1007/s10555-006-9032-0",
language = "English (US)",
volume = "25",
pages = "589--600",
journal = "Cancer and Metastasis Reviews",
issn = "0167-7659",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone

AU - Pratap, J.

AU - Lian, J. B.

AU - Javed, A.

AU - Barnes, G. L.

AU - van Wijnen, Andre J

AU - Stein, J. L.

AU - Stein, G. S.

PY - 2006/12

Y1 - 2006/12

N2 - 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/TGFβ 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.

AB - 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/TGFβ 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.

KW - Bone metastasis

KW - Breast cancer

KW - Osteolysis

KW - Osteolytic disease

KW - Prostate cancer

KW - Smads

UR - http://www.scopus.com/inward/record.url?scp=33846034921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846034921&partnerID=8YFLogxK

U2 - 10.1007/s10555-006-9032-0

DO - 10.1007/s10555-006-9032-0

M3 - Article

C2 - 17165130

AN - SCOPUS:33846034921

VL - 25

SP - 589

EP - 600

JO - Cancer and Metastasis Reviews

JF - Cancer and Metastasis Reviews

SN - 0167-7659

IS - 4

ER -