Abstract
RUNX2 is a transcription factor playing the major role in osteogenesis, but it can be involved in DNA damage response, which is crucial for cancer transformation. RUNX2 can interact with cell cycle regulators: cyclin-dependent kinases, pRB and p21Cip1 proteins, as well as the master regulator of the cell cycle, the p53 tumor suppressor. RUNX2 is involved in many signaling pathways, including those important for estrogen signaling, which, in turn, are significant for breast carcinogenesis. RUNX2 can promote breast cancer development through Wnt and Tgfβ signaling pathways, especially in estrogen receptor (ER)-negative cases. ERα interacts directly with RUNX2 and regulates its activity. Moreover, the ERα gene has a RUNX2 binding site within its promoter. RUNX2 stimulates the expression of aromatase, an estrogen producing enzyme, increasing the level of estrogens, which in turn stimulate cell proliferation and replication errors, which can be turned into carcinogenic mutations. Exploring the role of RUNX2 in the pathogenesis of breast cancer can lead to revealing new therapeutic targets.
Highlights
RUNX2 is a transcription factor playing the major role in osteogenesis, but it can be involved in DNA damage response, which is crucial for cancer transformation
A weaker association and limited epidemiological data are available on estrogen and ovarian cancer, which has the highest mortality among gynaecological cancers [1,5]
Each RUNX member contains a transactivation and an inhibitory domain (ID), both located at the C-terminal part, PPxY (PY) motif enabling RUNX to interact with peptides containing WW domain, and VWRPY motif interacting with the WD domain of Groucho/TLE family transcription co-repressors [34,39]
Summary
Some cancers respond to hormonal signals, expressing high level of hormone receptors and they are called hormone-dependent cancers. A weaker association and limited epidemiological data are available on estrogen and ovarian cancer, which has the highest mortality among gynaecological cancers [1,5] Another group of estrogen-related cancers are endocrine gland cancers, originating from adrenocortical, pancreatic, prostate and thyroid tissues. Male-specific prostate cancer has been included in estrogen-dependent cancers group It affect individuals of advanced age, when the production of testosterone declined, while estrogen levels remain stable or even rise. It seems that high estrogen/testosterone ratio is a key factor for prostate cancer development [7]. It is the second most common cancer in males, and its incidence between populations varies greatly worldwide [8]
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