Lrp8-KO Mouse

Lrp8, also known as low-density lipoprotein receptor-related protein 8, is a cell membrane receptor belonging to the LDL receptor family. It is involved in multiple biological processes. For example, it serves as the selenoprotein P (SELENOP) receptor, playing a role in selenocysteine uptake, which is crucial for the translation of antiferroptotic selenoprotein GPX4 [1]. It is also associated with pathways like those related to β-catenin, STAT3, and p53 signaling, influencing cell proliferation, apoptosis, and stemness [2,3,4].

Genetic deletion of Lrp8 in MYCN-amplified neuroblastoma cells leads to ferroptosis due to insufficient selenocysteine supply, as alternative selenium uptake pathways are low-expressed. This identifies Lrp8 as a targetable vulnerability in this cancer type [1]. In gastric cancer, silencing Lrp8 affects tumor spheroid formation and proliferation, while its overexpression promotes β-catenin nuclear translocation, cancer cell proliferation, and stemness [2]. In osteosarcoma, blocking Lrp8 inhibits cell proliferation and induces apoptosis by affecting the Lrp8/STAT3/PD-L1 network [3]. In ovarian cancer, Lrp8 knockdown reduces cell proliferation, migration, and promotes apoptosis, with the p53 signaling pathway involved [4].

In summary, Lrp8 is involved in various biological functions related to cell survival, proliferation, and apoptosis. Studies using gene knockout models have revealed its significance in multiple cancer types, such as MYCN-amplified neuroblastoma, gastric cancer, osteosarcoma, and ovarian cancer. These findings suggest Lrp8 could be a potential therapeutic target in these diseases.

References:

1. Alborzinia, Hamed, Chen, Zhiyi, Yildiz, Umut, Trumpp, Andreas, Friedmann Angeli, José Pedro. 2023. LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma. In EMBO molecular medicine, 15, e18014. doi:10.15252/emmm.202318014. https://pubmed.ncbi.nlm.nih.gov/37435859/

2. Liu, Bin, Bukhari, Ihtisham, Li, Fazhan, Mi, Yang, Zheng, Peng-Yuan. 2024. Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation. In Journal of advanced research, 69, 299-312. doi:10.1016/j.jare.2024.04.002. https://pubmed.ncbi.nlm.nih.gov/38609049/

3. Zheng, Shiqin, Wei, Yuxi, Jiang, Yu, Hao, Yi. 2020. LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma. In Tumori, 107, 238-246. doi:10.1177/0300891620952872. https://pubmed.ncbi.nlm.nih.gov/33054597/

4. Xu, Yan, Zhou, Yang, Yi, Xiling, Nie, Xiaocui. 2024. LRP8 promotes tumorigenesis in ovarian cancer through inhibiting p53 signaling. In Cell biology international, 48, 626-637. doi:10.1002/cbin.12133. https://pubmed.ncbi.nlm.nih.gov/38263609/