MilliporeSigma
  • EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.

EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.

Communications biology (2023-07-21)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Sigma-Aldrich
Leupeptin, microbial, ≥90% (HPLC)
Sigma-Aldrich
Cycloheximide, from microbial, ≥94% (TLC)
Sigma-Aldrich
G 418 disulfate salt, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Aprotinin from bovine lung, lyophilized powder, 3-8 TIU/mg solid