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Tuesday, October 15th, 2024
Centre de recherche - Paris - Amphith√©√Ętre Marie Curie

Endocytic control of cell plasticity in cancer

Over the past two decades, there has been a significant shift in our understanding of the role of endocytosis and trafficking of signaling receptors. It has evolved from being viewed simply as a signal extinguisher (resulting in long-term attenuation) to being recognized as a sophisticated mechanism capable of delivering signals to specific cellular locations with precise timing. Therefore, endocytosis functions as a regulatory program that impacts various aspects of cell physiology, and we have evidence suggesting that alterations in this program may be causal and targetable in cancer. On the one hand, by exploiting the EGFR model system, we obtained confirmation that the integration of the two functions of endocytosis (sustainment and attenuation of signals) might be achieved, at least in part, at the plasma membrane (PM) by activation of different endocytic routes. Disruption of this balance appears to contribute significantly to cancer cell proliferation, invasion, and metastasis. On the other hand, our research has demonstrated the causal role of an endocytic protein, Epsin3 (EPN3), in breast cancer development, particularly in association with the emergence of partial epithelial-to-mesenchymal transition (pEMT), cancer stem cells, and invasive phenotypes. Increased E-cadherin endocytosis is the initial event driving EPN3-induced pEMT, that render cells more plastic and prone to metastatic dissemination. Importantly, inhibition of increased E-Cadherin endocytosis is capable of reversing EPN3-dependent invasiveness. The restricted expression of EPN3 in adult tissues, along with its overexpression in breast cancer, positions EPN3-drived endocytosis as a promising target for therapeutic intervention.


Prof. Sara Lucia Giustina Sigismund
University of Milan, European Institute of Oncology, Milan, Italy

Invited by

Dr. Ludger Johannes
Chimie et Biologie de la Cellule (UMR3666 / U1143)

Institut Curie