Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance
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Aysegül Kaymak1, Sergi Sayols2, Thaleia Papadopoulou1,3 and Holger Richly1
1Laboratory of Molecular Epigenetics, Institute of Molecular Biology, Mainz, Germany
2Bioinformatics Core Facility, Institute of Molecular Biology, Mainz, Germany
3Department of Developmental and Stem Cell Biology, Institute Pasteur, Paris, France
Holger Richly, email: [email protected]
Keywords: breast cancer; metastasis; cell invasion
Received: October 17, 2017 Accepted: May 24, 2018 Published: June 19, 2018
Breast cancer is one of the most common malignancies among women which is often treated with hormone therapy and chemotherapy. Despite the improvements in detection and treatment of breast cancer, the vast majority of breast cancer patients are diagnosed with metastatic disease either at the beginning of the disease or later during treatment. Still, the molecular mechanisms causing a therapy resistant metastatic breast cancer are still elusive. In the present study we addressed the function of the transcriptional activator ZRF1 during breast cancer progression. We provide evidence that ZRF1 plays an essential role for the early metastatic events in vitro and acts like a tumor suppressor protein during the progression of breast invasive ductal carcinoma into a more advanced stage. Hence, depletion of ZRF1 results in the acquisition of metastatic behavior by facilitating the initiation of the metastatic cascade, notably for cell adhesion, migration and invasion. Furthermore absence of ZRF1 provokes endocrine resistance via misregulation of cell death and cell survival related pathways. Taken together, we have identified ZRF1 as an important regulator of breast cancer progression that holds the potential to be explored for new treatment strategies in the future.
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