First name
Claudia
Last name
Iavarone
Year of Study
Thesis Title
Functional characterization of the endocytic protein Epsin3 in breast cancer
Thesis Abstract
Endocytosis plays a critical role in the maintenance of cellular homeostasis.
One relevant, unanswered, question regarding the role of endocytosis in the cell is whether subversion of the endocytic route is involved in the development of pathological conditions, such as cancer. This possibility is supported by studies showing altered expression of several endocytic proteinsin human tumors. In a previous study in our lab, the endocytic protein Epsin3 (Epn3) was found in a gene signature prognostic for metastatic breast cancer. Epn3 belongs to the Epsin family of endocytic proteins. Unlike the other Epsin members, which are ubiquitously expressed, Epn3 is exclusively expressed in gastric cells and in wounded or pathological tissues. While Epn1 and Epn2 have been well characterized as endocytic adaptors, the exact function of Epn3 protein in endocytosis is largely unknown.
In the present study, we show that Epn3 is overexpressed in breast tumors and that its up regulation correlates with clinical parameters of aggressive disease. We demonstrate that breast tumor cells harboring Epn3 amplification are dependent on Epn3 deregulation for the maintenance of their tumorigenic potential. Furthermore, overexpression of Epn3 in breast tumor cells increases the tumorigenic potential in vivo. Of note, Epn3 overexpression is able to induce transcriptional and morphological changes typical of an epithelial-to-mesenchymal transition (EMT), in a TGFβdependent manner. Finally, we demonstrate that Epn3 is involved in Ecadherin Internalization, by inducing its down regulation from the cell surface upon TGFβ-stimulation. In conclusion, our data suggest a novel oncogenic role for Epn3 in Human breast cancer.
One relevant, unanswered, question regarding the role of endocytosis in the cell is whether subversion of the endocytic route is involved in the development of pathological conditions, such as cancer. This possibility is supported by studies showing altered expression of several endocytic proteinsin human tumors. In a previous study in our lab, the endocytic protein Epsin3 (Epn3) was found in a gene signature prognostic for metastatic breast cancer. Epn3 belongs to the Epsin family of endocytic proteins. Unlike the other Epsin members, which are ubiquitously expressed, Epn3 is exclusively expressed in gastric cells and in wounded or pathological tissues. While Epn1 and Epn2 have been well characterized as endocytic adaptors, the exact function of Epn3 protein in endocytosis is largely unknown.
In the present study, we show that Epn3 is overexpressed in breast tumors and that its up regulation correlates with clinical parameters of aggressive disease. We demonstrate that breast tumor cells harboring Epn3 amplification are dependent on Epn3 deregulation for the maintenance of their tumorigenic potential. Furthermore, overexpression of Epn3 in breast tumor cells increases the tumorigenic potential in vivo. Of note, Epn3 overexpression is able to induce transcriptional and morphological changes typical of an epithelial-to-mesenchymal transition (EMT), in a TGFβdependent manner. Finally, we demonstrate that Epn3 is involved in Ecadherin Internalization, by inducing its down regulation from the cell surface upon TGFβ-stimulation. In conclusion, our data suggest a novel oncogenic role for Epn3 in Human breast cancer.
Students representatives
Off
Curricula Term