Irs1-KO Mouse

Irs1, or Insulin receptor substrate 1, is an important signal transduction adapter. It is crucial for extracellular signal transduction from insulin-like growth factor-1 receptor and its family members to downstream proteins, and is involved in the insulin signaling pathway [1,4,5]. This gene plays a significant role in various biological processes, and its dysregulation is associated with diseases like cancer and type 2 diabetes [1,2,3,4].

In cancer, Irs1 has been implicated in tumorigenesis and metastasis. In thyroid cancer, it is highly expressed, promoting metastasis through epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway [1]. In oral squamous cell carcinoma (OSCC), Irs1 is also highly expressed, and its silencing inhibits cell proliferation, induces apoptosis, and hinders EMT through the p53/Line-1 signaling pathway [2]. In ovarian cancer, repressing Irs1/2 by NT157 inhibits malignant behaviors by inactivating the PI3K/AKT/mTOR pathway and inducing autophagy [3]. Moreover, in esophageal squamous cell carcinoma, the decreased expression of Irs1 is related to lymph node metastases and is a predictor of poor overall survival [6]. In type 2 diabetes, mutations in the Irs1 gene and certain genotypes are associated with the disease [4].

In conclusion, Irs1 is essential in the insulin signaling pathway. Its dysregulation is closely linked to cancer metastasis and type 2 diabetes. Studies on Irs1, especially through gene-related models, contribute to understanding the mechanisms of these diseases, potentially providing new strategies for diagnosis and treatment.

References:

1. Yu, Fang, Huang, Dongdong, Kuang, Yeye, Zhou, Jie, Teng, Xiaodong. 2024. IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways. In Clinical endocrinology, 100, 284-293. doi:10.1111/cen.15005. https://pubmed.ncbi.nlm.nih.gov/38172081/

2. Xiao, Yanbo, Zhu, Xuan, Li, Qun, Liu, Xun, Tan, Jin. . m6A-Mediated IRS1 Regulates the Development of Oral Squamous Cell Carcinoma through p53/Line-1 Signaling. In Frontiers in bioscience (Landmark edition), 29, 257. doi:10.31083/j.fbl2907257. https://pubmed.ncbi.nlm.nih.gov/39082352/

3. Li, Cai-Xia, Men, Chuan-Di, Yang, Wei-Hong, Zhu, Ji-Hui, Cheng, Zhong-Ping. 2023. Repressing IRS1/2 by NT157 inhibits the malignant behaviors of ovarian cancer through inactivating PI3K/AKT/mTOR pathway and inducing autophagy. In The Kaohsiung journal of medical sciences, 39, 377-389. doi:10.1002/kjm2.12652. https://pubmed.ncbi.nlm.nih.gov/36727938/

4. Keshavarzi, Fatemeh, Golsheh, Shadi. 2019. IRS1- rs10498210 G/A and CCR5-59029 A/G polymorphisms in patients with type 2 diabetes in Kurdistan. In Molecular genetics & genomic medicine, 7, e631. doi:10.1002/mgg3.631. https://pubmed.ncbi.nlm.nih.gov/30884193/

5. Copps, K D, White, M F. 2012. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. In Diabetologia, 55, 2565-2582. doi:10.1007/s00125-012-2644-8. https://pubmed.ncbi.nlm.nih.gov/22869320/

6. Lei, Yufei, Jamal, Muhammad, Zeng, Xingruo, Xie, Songping, Zhang, Qiuping. 2022. Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma. In Gene, 835, 146651. doi:10.1016/j.gene.2022.146651. https://pubmed.ncbi.nlm.nih.gov/35688292/