Contemplations on MDMX (MDM4) driving triple negative breast cancer circulating tumor cells and metastasis
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Chong Gao1,2, Gu Xiao1 and Jill Bargonetti1,2,3
1 The Department of Biological Sciences at Hunter College, Belfer Building, City University of New York, New York, NY, USA
2 The Graduate Center Biology Program of City University of New York, New York, NY, USA
3 Department of Cell and Developmental Biology, Weill Cornell Medical College New York, New York, NY, USA
Keywords: MDMX; MDM4; mutant p53; mtp53; metastasis
Received: July 11, 2019 Accepted: July 16, 2019 Published: August 20, 2019
MDMX (MDM4) is emerging as an important breast cancer (BC) biomarker, and oncoprotein, that can be targeted in combination with its well-known family member MDM2. While MDM2 has previously been implicated in driving BC metastasis, information about the role of MDMX in driving circulating tumor cells (CTCs) and BC metastasis is lacking. BCs often have alterations of MDM2, MDMX, and mutant p53 (mtp53). Therefore, the role of MDM2 and MDMX in the context of mtp53 in BCs requires further clarification. Our group has recently reported that triple negative breast cancer (TNBC) metastasis is dependent on both MDM2 and MDMX, and depleting MDM2 results in increased MDMX, but depleting MDMX does not cause an increase in MDM2. In the context of human TNBC expressing mtp53 in an orthotopic mouse model the down-regulation of MDMX virtually cleared CTCs from the blood. Contemplations, using the available literature, suggest that disrupting the stability and/or function of MDMX protein (and its downstream targets), in the context of mtp53 expressing BCs, might be beneficial for patient survival. It remains to be determined if blocking mtp53-MDMX pathways can inhibit early stage TNBC and eliminate CTCs that have the potential to form metastatic lesions.
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