Ptprk-KO Mouse

Ptprk, or Protein Tyrosine Phosphatase Receptor Type K, is a receptor tyrosine phosphatase linked to the regulation of growth factor signalling, cell-cell adhesion, and tumour suppression [4]. It is involved in multiple biological pathways, such as the Wnt signalling pathway by regulating ZNRF3, a transmembrane E3 ubiquitin ligase that targets Wnt receptors for degradation [5,6].

In obesity, high-fat-fed PTPRK knockout male and female mice have lower weight gain and reduced hepatic fat accumulation. PTPRK in hepatocytes is found to regulate glycolysis and de novo lipogenesis, promoting hepatocyte metabolic reprogramming, and its silencing in liver cancer cell lines reduces colony-forming capacity [1]. In celiac disease (CeD), PTPRK levels are reduced in biopsies and organoids, and modulating its levels can impact the phosphorylation of EGFR and ERK, as well as cell proliferation [2]. In colon cancer, knockdown of PTPRK potentiates the pro-oncogenic CD133-AKT pathway and reduces sensitivity to oxaliplatin [3]. PTPRK also promotes intestinal repair in vivo and suppresses tumour growth in the mouse colon and colorectal cancer xenografts, independent of its catalytic function [4]. In ovarian cancer cell lines, PTPRK expression is downregulated in drug-resistant cells, especially in ALDH1A1-positive cancer stem-like cells [7]. In NSCLC, downregulation of PTPRK promotes cell proliferation and metastasis by enhancing STAT3 activation [8]. In Han Chinese women, PTPRK appears to be a susceptibility gene for preeclampsia, with higher expression in preeclamptic placentas [9].

In summary, Ptprk plays crucial roles in metabolism, cell proliferation, adhesion, and tumour suppression across various biological processes and disease conditions. Studies using gene knockout mouse models have revealed its functions in obesity-related hepatic metabolism, celiac disease, colon cancer, intestinal repair, ovarian cancer drug resistance, NSCLC, and preeclampsia, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Gilglioni, Eduardo H, Li, Ao, St-Pierre-Wijckmans, Wadsen, Wu, Wei, Gurzov, Esteban N. 2024. PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity. In Nature communications, 15, 9522. doi:10.1038/s41467-024-53733-0. https://pubmed.ncbi.nlm.nih.gov/39496584/

2. Nanayakkara, Merlin, Bellomo, Claudia, Furone, Francesca, Auricchio, Salvatore, Barone, Maria Vittoria. 2022. PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids. In Cells, 12, . doi:10.3390/cells12010115. https://pubmed.ncbi.nlm.nih.gov/36611909/

3. Matsushita, Masashi, Mori, Yusuke, Uchiumi, Kyosuke, Shimozato, Osamu, Ozaki, Toshinori. 2019. PTPRK suppresses progression and chemo-resistance of colon cancer cells via direct inhibition of pro-oncogenic CD133. In FEBS open bio, 9, 935-946. doi:10.1002/2211-5463.12636. https://pubmed.ncbi.nlm.nih.gov/30947381/

4. Young, Katherine A, Wojdyla, Katarzyna, Lai, Tiffany, Fearnley, Gareth W, Sharpe, Hayley J. 2024. The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression. In Journal of cell science, 137, . doi:10.1242/jcs.261914. https://pubmed.ncbi.nlm.nih.gov/38904097/

5. Kim, Minseong, Reinhard, Carmen, Niehrs, Christof. 2021. A MET-PTPRK kinase-phosphatase rheostat controls ZNRF3 and Wnt signaling. In eLife, 10, . doi:10.7554/eLife.70885. https://pubmed.ncbi.nlm.nih.gov/34590584/

6. Chang, Ling-Shih, Kim, Minseong, Glinka, Andrey, Reinhard, Carmen, Niehrs, Christof. 2020. The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer. In eLife, 9, . doi:10.7554/eLife.51248. https://pubmed.ncbi.nlm.nih.gov/31934854/

7. Świerczewska, Monika, Sterzyńska, Karolina, Wojtowicz, Karolina, Zabel, Maciej, Januchowski, Radosław. 2019. PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations. In International journal of molecular sciences, 20, . doi:10.3390/ijms20082053. https://pubmed.ncbi.nlm.nih.gov/31027318/

8. Xu, Xuting, Li, Dong, Liu, Jin, Dai, Licheng, Dong, Shunli. 2019. Downregulation of PTPRK Promotes Cell Proliferation and Metastasis of NSCLC by Enhancing STAT3 Activation. In Analytical cellular pathology (Amsterdam), 2019, 4265040. doi:10.1155/2019/4265040. https://pubmed.ncbi.nlm.nih.gov/30838170/

9. Li, Huihui, Yan, Xingyu, Yang, Man, Li, Wei-Ping, Zhang, Cong. 2021. The Impact of PTPRK and ROS1 Polymorphisms on the Preeclampsia Risk in Han Chinese Women. In International journal of hypertension, 2021, 3275081. doi:10.1155/2021/3275081. https://pubmed.ncbi.nlm.nih.gov/34646579/