Identification of the Role of MnSOD in EGFR-Positive Breast Cancer Development

摘要

Sprouty(Spry) was identified as a general inhibitor of receptor tyrosine kinases in Drosophila including FGFR and EGFR signaling. The mammalian genome contains four Spry genes (Spryl-4). Among these, Spry2 encodes a protein that displays the highest degree of homology with dSpry. Recently, it has been shown that hSpry1 and hSpry2 are downregulated - in breast cancer, suggesting a role for Spry in modulating the growth properties of breast cancer cells. - To investigate the role of hSpry2 in EGFR signaling, we have analyzed the effect of ectopic expression of hspry2 on EG%R trafficking. hspry2 resides in the trans-Golgi network (TGN) and is targeted to early endosomes via a process that is dependent on its ubiquitination. Upon reaching the early endosome, hspry2 interacts with ubiquitin receptors that control the endosomal sorting of internalized growth factor receptors, thereby preventing further progression of EGFR along the endocytic sorting process. Our data indicate that hspry2 may influence the signaling capacity of EGFR by altering its endocytic fate. The relevance of this mechanism to the link between EGFR activity and the development of breast cancer is under investigation.