Igf1r, the insulin-like growth factor 1 receptor, is a cell-surface, tyrosine-kinase-containing heterotetramer. It mediates the biological activities of insulin-like growth factors (IGFs), which are crucial for various cellular functions such as anti-apoptosis and cell survival. The IGF1R is linked to numerous cytoplasmic signaling cascades, like the PI3K-AKT pathway, and is of great importance in normal development as well as in disease states, especially cancer [3]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying Igf1r function.

In cancer research, IGF1R has been identified as a candidate therapeutic target. In colorectal cancer, IGF1R expression is increased, and it serves as a receptor for CAF-secreted IGF2, promoting tumor growth, migration, and invasion. The IGF2-IGF1R signaling mediates oncogenic effects through the YAP1-target signature, and targeting IGF1R and YAP1 together enhances antitumor effects [2]. In triple-negative breast cancer, phosphorylation of IGF1R correlates with reduced autophagy, an unfavorable local immune profile, and poor prognosis, suggesting that IGF1R inhibition may be a novel treatment strategy [4]. In non-small cell lung cancer, the circ_PPAPDC1A/miR-30a-3p/IGF1R axis activates the PI3K/AKT/mTOR signaling pathway, promoting Osimertinib resistance [6]. In addition, IGF1R has been found to be an entry receptor for respiratory syncytial virus, triggering a cellular signaling cascade that recruits nucleolin to the plasma membrane for viral entry [1]. In pancreatic β-cells, decreased Igf1r signaling attenuates senescence and improves function, with implications for type 2 diabetes [5].

In conclusion, Igf1r plays essential roles in multiple biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has significantly contributed to understanding its functions in cancer, viral infections, and diabetes-related β-cell dysfunction. These findings highlight Igf1r as a potential therapeutic target in various diseases.

References:

1. Griffiths, Cameron D, Bilawchuk, Leanne M, McDonough, John E, Moraes, Theo J, Marchant, David J. 2020. IGF1R is an entry receptor for respiratory syncytial virus. In Nature, 583, 615-619. doi:10.1038/s41586-020-2369-7. https://pubmed.ncbi.nlm.nih.gov/32494007/

2. Zhang, Jinglin, Chen, Bonan, Li, Hui, Lo, Kwok Wai, Kang, Wei. 2022. Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways. In The Journal of pathology, 259, 205-219. doi:10.1002/path.6033. https://pubmed.ncbi.nlm.nih.gov/36373776/

3. Werner, Haim, Sarfstein, Rive, Bruchim, Ilan. 2019. Investigational IGF1R inhibitors in early stage clinical trials for cancer therapy. In Expert opinion on investigational drugs, 28, 1101-1112. doi:10.1080/13543784.2019.1694660. https://pubmed.ncbi.nlm.nih.gov/31731883/

4. Wu, Qi, Tian, Ai-Ling, Kroemer, Guido, Kepp, Oliver. 2021. Autophagy induction by IGF1R inhibition with picropodophyllin and linsitinib. In Autophagy, 17, 2046-2047. doi:10.1080/15548627.2021.1936934. https://pubmed.ncbi.nlm.nih.gov/34110249/

5. Iwasaki, Kanako, Lalani, Benjamin, Kahng, Jiho, Kulkarni, Rohit N, Aguayo-Mazzucato, Cristina. 2023. Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells. In Frontiers in endocrinology, 14, 1203534. doi:10.3389/fendo.2023.1203534. https://pubmed.ncbi.nlm.nih.gov/37441495/

6. Tang, Yi-Fang, Liu, Zheng-Hua, Zhang, Lei-Yi, Hu, Chun-Hong, Zou, Fang-Wen. 2024. circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC). In Molecular cancer, 23, 91. doi:10.1186/s12943-024-01998-w. https://pubmed.ncbi.nlm.nih.gov/38715012/