Nuclear IGF1R interacts with NuMA and regulates 53BP1dependent DNA doublestrand break repair in colorectal cancer.
Oncol Rep
; 46(2)2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34165167
ABSTRACT
Nuclear insulinlike 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, immunoprecipitationcoupled mass spectrometry was performed in an IGF1Roverexpressing SW480OE 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 doublestrand 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 p53binding protein 1 (53BP1)NuMA colocalization between IGF1Rpositive (R+) and IGF1Rnegative (R) mouse embryonic fibroblasts following exposure to ionizing radiation (IR). 53BP1 was retained by NuMA in the R cells during IRinduced DNA damage. By contrast, the level of NuMA53BP1 was markedly lower in R+ cells compared with R cells. The present data suggested a regulatory role of nIGF1R in 53BP1dependent DSB repair through its interaction with NuMA. Brightfield PLA analysis on a paraffinembedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1dependent DDR by regulating the NuMA53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Cell Nucleus
/
Receptor, IGF Type 1
/
Cell Cycle Proteins
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Tumor Suppressor p53-Binding Protein 1
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article