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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 IGF...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250583/ https://www.ncbi.nlm.nih.gov/pubmed/34165167 http://dx.doi.org/10.3892/or.2021.8119 |
Sumario: | 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. |
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