Rptor-KO Mouse

RPTOR, the regulatory associated protein of MTOR complex 1, is a key component in the mTOR pathway. This pathway is central in promoting cell growth in response to various factors like insulin, energy levels, and amino acids [3,5]. RPTOR is involved in regulating autophagy, a cellular catabolic process, and has a significant impact on maintaining cellular homeostasis [3]. Genetic models, such as gene knockout and conditional knockout mouse models, are valuable tools for studying RPTOR's functions.

In esophageal squamous cell carcinoma (ESCC), METTL1 or WDR4 knockdown reduces the translation of a subset of oncogenic transcripts enriched in the RPTOR/ULK1/autophagy pathway, indicating RPTOR's role in ESCC tumorigenesis [1]. In non-small cell lung cancer (NSCLC) brain metastasis, RPTOR is upregulated, increasing blood-brain barrier permeability, and its blockade suppresses BM by interfering with ceramide metabolism [2]. In melanoma, RPTOR-mutation patients have prolonged overall survival and a higher objective response rate to immune checkpoint inhibitors compared to RPTOR-wildtype patients, suggesting it could be a biomarker for immunotherapy efficacy [4].

In summary, RPTOR is crucial in multiple biological processes, especially in regulating autophagy. Studies using KO/CKO mouse models have revealed its significance in diseases like ESCC, NSCLC brain metastasis, and melanoma. These findings provide potential therapeutic targets and biomarkers for these diseases.

References:

1. Han, Hui, Yang, Chunlong, Ma, Jieyi, Choe, Junho, Lin, Shuibin. 2022. N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis. In Nature communications, 13, 1478. doi:10.1038/s41467-022-29125-7. https://pubmed.ncbi.nlm.nih.gov/35304469/

2. Lin, Ying, Wu, Yun, Zhang, Qiangzu, Chen, Yusheng, Li, Hongru. 2024. RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding. In Journal of experimental & clinical cancer research : CR, 43, 1. doi:10.1186/s13046-023-02874-z. https://pubmed.ncbi.nlm.nih.gov/38163890/

3. Foerster, Elisabeth G, Mukherjee, Tapas, Cabral-Fernandes, Liliane, Girardin, Stephen E, Philpott, Dana J. 2021. How autophagy controls the intestinal epithelial barrier. In Autophagy, 18, 86-103. doi:10.1080/15548627.2021.1909406. https://pubmed.ncbi.nlm.nih.gov/33906557/

4. Jiang, Yanfang, Hu, Xintong, Wang, Zhouyu, Chen, Dongsheng, Zhao, Pingwei. 2023. RPTOR mutation: a novel predictor of efficacious immunotherapy in melanoma. In Investigational new drugs, 42, 60-69. doi:10.1007/s10637-023-01413-z. https://pubmed.ncbi.nlm.nih.gov/38071684/

5. Sancak, Yasemin, Peterson, Timothy R, Shaul, Yoav D, Bar-Peled, Liron, Sabatini, David M. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. In Science (New York, N.Y.), 320, 1496-501. doi:10.1126/science.1157535. https://pubmed.ncbi.nlm.nih.gov/18497260/