IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits

• Published in: Discover. Oncology Vol. 12; no. 1; p. 13
• Main Authors: Mills, Jack V., Osher, Eliot, Rieunier, Guillaume, Mills, Ian G., Macaulay, Valentine M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2021; Springer Nature B.V
• Subjects: Antibodies; Binding sites; Biology; Brief Communication; Cancer Research; Insulin-like growth factors; Internal Medicine; Kinases; Laboratories; Medical research; Medicine; Medicine & Public Health; Molecular Medicine; Oncology; Prostate cancer; Proteins; Radiotherapy; Reagents; RNA polymerase; Surgical Oncology; United Kingdom > UK
• ISSN: 2730-6011; 2730-6011
• DOI: 10.1007/s12672-021-00407-8

Mature type 1 insulin-like growth factor receptors (IGF-1Rs) are heterotetrameric structures comprising two extracellular α-subunits disulphide-bonded to two transmembrane β-subunits with tyrosine kinase activity. IGF-1R is a well-known cell surface mediator of malignant growth, with an incompletely understood role upon nuclear import as a transcriptional regulator. Previous characterisation of nuclear IGF-1R focused on IGF-1Rβ. Here, we aimed to clarify the source of nuclear IGF-1R and investigate whether α-subunits contribute to nuclear IGF-1R function. Using prostate cancer cell lines DU145 and 22Rv1 we detected nuclear α- and β-subunits, with increase in nuclear signal upon IGF-treatment and reduction in response to IGF-1R inhibitor BMS-754807. Following biotinylation of cell surface proteins, biotinylated α- and β-subunits were detected in nuclear extracts of both cell lines. Furthermore, α- and β-subunits reciprocally co-precipitated from nuclear extract. Finally, we detected recruitment of both subunits to regulatory regions of chromatin, including the promoter of the oncogene JUN , that we previously identified in ChIP-seq as sites of IGF-1Rβ enrichment. These data confirm the cell surface origin of nuclear IGF-1R, suggest the presence of nuclear αβ complexes and reveal that both IGF-1Rα- and β-subunits contribute to pro-tumorigenic functions of nuclear IGF-1R.