Metastatic dissemination is the main cause of cancer-related death. However, the underlying molecular mechanisms are still poorly understood.
Thanks to an AIRC grant, Sara Sigismund, researcher of the DEO, will shed light on critical cell mechanisms of metastatic dissemination in breast cancer.
One of the main mechanisms known to regulate metastasis formation is the so-called epithelial-to-mesenchymal transition (EMT), namely the ability of cancer cells to switch between a proliferative (or epithelial) and an invasive (or mesenchymal) state. Through EMT, cancer cells acquire the ability to invade the surrounding tissue, move into the blood vessels and, as circulating tumor cells, travel in the bloodstream to reach and colonize distant sites in the body. Partial EMT, meaning an intermediate state in which cancer cells show at the same time both traits of invasive and proliferative cells, makes cells extremely prone to form metastases. Partial EMT is linked to the re-localization, through a process called endocytosis, of proteins typically expressed by proliferative/epithelial cells, such as E-Cadherin.
Epsin3 protein is involved in endocytosis and, by regulating E-Cadherin re-localization, elicits partial EMT, thus inducing invasive features in breast cells. Moreover, Epsin3 is overexpressed in breast cancer and its overexpression has been associated with metastasis and poor prognosis of breast cancer patients.
What are the molecular mechanisms through which Epsin3 modulates E-Cadherin re-localization, inducing partial EMT and ultimately metastasis formation? What is the role of Epsin3 in breast cancer progression? What is the role of Epsin3 in the appearance of circulating tumor cells, metastases and therapy resistance?
This grant will enable Sara Sigismund and her group to answer these questions, shedding light on critical mechanisms –related to Epsin3-regulated E-Cadherin endocytosis– of metastatic dissemination in breast cancer. Importantly, these studies will assess whether Epsin3 may represent a novel therapeutic target in the fight against breast cancer progression and metastatic dissemination.