Igf2, insulin-like growth factor 2, is a paternally expressed growth-promoting gene [2]. It plays a crucial role in embryonic growth and development, as well as in adult physiology [6]. The protein is involved in multiple signaling pathways, such as the IGF2-IGF1R pathway which has been implicated in cancer progression [3,4]. Animal models, especially knockout mouse models, have been instrumental in understanding its complex regulation and functions [1].

In the context of human disorders, mutations in Igf2 have been associated with Silver-Russell syndrome (SRS). All the SRS-related Igf2 mutations reported reside on the paternally inherited allele, and patients with these mutations present with specific phenotypes like feeding difficulty, reduced body mass index, and mild relative macrocephaly [2]. In cancer, overexpression of Igf2 is an accepted risk factor for colorectal cancer (CRC) development. Loss of imprinting of Igf2 can lead to its overexpression, increased cell proliferation, and CRC development. In adrenocortical carcinoma, Igf2 expression differentiates it from adenomas, and different Igf2 concentrations influence cancer cell proliferation, metabolism, and viability [5,7].

In conclusion, Igf2 is essential for growth and development. Studies using knockout mouse models have revealed its role in growth regulation, especially prenatal growth, and its implications in diseases such as SRS and various cancers including CRC and adrenocortical carcinoma. Understanding Igf2 provides insights into the mechanisms of growth-related disorders and cancer pathogenesis, which may potentially lead to new therapeutic strategies.

References:

1. Sélénou, Céline, Brioude, Frédéric, Giabicani, Eloïse, Sobrier, Marie-Laure, Netchine, Irène. 2022. IGF2: Development, Genetic and Epigenetic Abnormalities. In Cells, 11, . doi:10.3390/cells11121886. https://pubmed.ncbi.nlm.nih.gov/35741015/

2. Masunaga, Yohei, Inoue, Takanobu, Yamoto, Kaori, Kagami, Masayo, Ogata, Tsutomu. . IGF2 Mutations. In The Journal of clinical endocrinology and metabolism, 105, . doi:10.1210/clinem/dgz034. https://pubmed.ncbi.nlm.nih.gov/31544945/

3. 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/

4. Andersson, Mattias K, Åman, Pierre, Stenman, Göran. 2019. IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors. In Cells, 8, . doi:10.3390/cells8080913. https://pubmed.ncbi.nlm.nih.gov/31426421/

5. Pereira, Sofia S, Monteiro, Mariana P, Costa, Madalena M, Jarak, Ivana, Pignatelli, Duarte. 2019. IGF2 role in adrenocortical carcinoma biology. In Endocrine, 66, 326-337. doi:10.1007/s12020-019-02033-5. https://pubmed.ncbi.nlm.nih.gov/31378849/

6. Potalitsyn, Pavlo, Mrázková, Lucie, Selicharová, Irena, Jiráček, Jiří, Žáková, Lenka. 2023. Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2. In Communications biology, 6, 863. doi:10.1038/s42003-023-05239-6. https://pubmed.ncbi.nlm.nih.gov/37598269/

7. Kasprzak, Aldona, Adamek, Agnieszka. 2019. Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer-From Basic Research to Potential Clinical Applications. In International journal of molecular sciences, 20, . doi:10.3390/ijms20194915. https://pubmed.ncbi.nlm.nih.gov/31623387/