| Title: |
EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis |
| Authors: |
Sukanya Chakraborty, Aaqib M. Bhat, Insha Mushtaq, Haitao Luan, Achyuth Kalluchi, Sameer Mirza, Matthew D. Storck, Nagendra Chaturvedi, Jose Antonio Lopez-Guerrero, Antonio Llombart-Bosch, Isidro Machado, Katia Scotlandi, Jane L. Meza, Gargi Ghosal, Donald W. Coulter, M. Jordan Rowley, Vimla Band, Bhopal C. Mohapatra, Hamid Band |
| Source: |
Communications Biology, Vol 6, Iss 1, Pp 1-21 (2023) |
| Publisher Information: |
Nature Portfolio, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
Abstract Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown. We establish that EHD1 is overexpressed in Ewing sarcoma (EWS), with high EHD1 mRNA expression specifying shorter patient survival. ShRNA-knockdown and CRISPR-knockout with mouse Ehd1 rescue established a requirement of EHD1 for tumorigenesis and metastasis. RTK antibody arrays identified IGF-1R as a target of EHD1 regulation in EWS. Mechanistically, we demonstrate a requirement of EHD1 for endocytic recycling and Golgi to plasma membrane traffic of IGF-1R to maintain its surface expression and downstream signaling. Conversely, EHD1 overexpression-dependent exaggerated oncogenic traits require IGF-1R expression and kinase activity. Our findings define the RTK traffic regulation as a proximal mechanism of EHD1 overexpression-dependent oncogenesis that impinges on IGF-1R in EWS, supporting the potential of IGF-1R and EHD1 co-targeting. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2399-3642 |
| Relation: |
https://doaj.org/toc/2399-3642 |
| DOI: |
10.1038/s42003-023-05125-1 |
| Access URL: |
https://doaj.org/article/09e76c7a25c7457f98d7a6fdc6e884ba |
| Accession Number: |
edsdoj.09e76c7a25c7457f98d7a6fdc6e884ba |
| Database: |
Directory of Open Access Journals |
