The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion [Molecular Bases of Disease]
December 23rd, 2014 by Shahi, P., Slorach, E. M., Wang, C.-Y., Chou, J., Lu, A., Ruderisch, A., Werb, Z.
The NET subfamily of zinc finger proteins is an important mediator during developmental processes. The evolutionary conserved zinc finger protein ZNF503/ Zeppo2 (zinc finger elbow-related proline domain protein-2; Zpo2) plays critical roles during embryogenesis. We have found that Zpo2 is expressed in adult tissue and have examined its function. We find that Zpo2 is a nuclear-targeted transcriptional repressor that is expressed in mammary epithelial cells. Elevated Zpo2 levels increase mammary epithelial cell proliferation. Zpo2 promotes cellular invasion through downregulation of E-cadherin and regulates the invasive phenotype in a Rac1-dependent manner. We detect elevated Zpo2 expression during breast cancer progression in MMTV-PyMT transgenic mouse model. Tumor transplant experiments indicated that overexpression of Zpo2 in MMTV-PyMT mammary tumor cell lines enhances lung metastasis. Our findings suggest that Zpo2 plays a significant role in mammary gland homeostasis and that deregulation of Zpo2 may promote breast cancer development.