Exploiting Nuclear Reprogramming Techniques to Dissect the Role Trophectoderm Epigenetic Reprogramming Plays during Breast Cancer Initiation, Invasion and Metastasis.

The American Cancer Society puts Breast cancer as the most common cancer in American women after skin cancer. Therefore, understanding in a deeper way how breast cancer is affected by epigenetic changes is of great importance. Epigenetic reprogramming is one of the hallmarks of cancer development that was shown to play a role during cancer initiation and, later on, when cells start to migrate and metastasize. Very recently, a global and robust epigenetic analysis revealed that cancer cells exhibit an epigenetic state that is equivalent to the epigenetic state of the trophectoderm (TE), a compartment of the early embryo that responsible for the formation of an extraembryonic tissue such as the placenta.

Here we aim to understand how a TE-like epigenetic state is achieved in normal and cancer cells and whether and when it is beneficial for cancer initiation, invasion and metastasis. We focus on breast cancer cells because they overexpress key TE transcription factors such as GATA3, EOMES and TFAP2C (GET). Importantly, this combination of factors was shown to induce a TE-like epigenetic state in somatic cells. We temporarily induce a TE-like epigenetic state by ectopic expressing the GET factors in human breast normal and cancer lines and in animal models to dissect how TE-like epigenetic state promotes cancer initiation and progression. This study will shed light on how a TE-like epigenetic reprogramming promotes breast cancer development and may suggest new therapeutic targets that mediate this effect.