Nuclear IGF1R interacts with NuMA and regulates 53BP1‑dependent DNA double‑strand break repair in colorectal cancer

Nuclear insulin‑like growth factor 1 receptor (nIGF1R) has been associated with poor overall survival and chemotherapy resistance in various types of cancer; however, the underlying mechanism remains unclear. In the present study, immunoprecipitation‑coupled mass spectrometry was performed in an IGF1R‑overexpressing SW480‑OE colorectal cancer cell line to identify the nIGF1R interactome. Network analysis revealed 197 proteins of interest which were involved in several biological pathways, including RNA processing, DNA double‑strand break (DSB) repair and SUMOylation pathways. Nuclear mitotic apparatus protein (NuMA) was identified as one of nIGF1R's colocalizing partners. Proximity ligation assay (PLA) revealed different levels of p53‑binding protein 1 (53BP1)‑NuMA colocalization between IGF1R‑positive (R⁺) and IGF1R‑negative (R^‑) mouse embryonic fibroblasts following exposure to ionizing radiation (IR). 53BP1 was retained by NuMA in the R^‑ cells during IR‑induced DNA damage. By contrast, the level of NuMA‑53BP1 was markedly lower in R⁺ cells compared with R^‑ cells. The present data suggested a regulatory role of nIGF1R in 53BP1‑dependent DSB repair through its interaction with NuMA. Bright‑field PLA analysis on a paraffin‑embedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA‑53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1‑dependent DDR by regulating the NuMA‑53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.