Krt17, a member of the intermediate filament family, is involved in various biological processes. It can regulate cell proliferation, migration, and has been associated with multiple signaling pathways like the PI3K-AKT pathway. It plays a role in maintaining the integrity of epithelial cells, protecting them from damage [4].

In colorectal cancer, Krt17 overexpression decreased xenograft tumor growth in immune-competent mice. T-cell depletion in a murine model showed that T lymphocytes were necessary for Krt17-mediated disruption of tumorigenesis. Krt17 caused YTHDF2 degradation through the ubiquitin-proteasome system, and CXCL10 was found to be the target gene of YTHDF2. Krt17 also synergized with anti-PD-1 for better tumor control in an immunotherapy-resistant murine model [1].

In idiopathic pulmonary fibrosis, airway basal cells from patients with IPF showed a KRT17highPTENlow dedifferentiated phenotype and promoted fibrosis. In vitro and in vivo studies with a SRC inhibitor saracatinib modified the profibrotic changes related to this phenotype [2].

In liver fibrosis, the expression of Krt17 was higher in fibrotic liver tissues of humans and mice. Krt17 promoted the activation of hepatic stellate cells (HSCs) via epithelial-mesenchymal transition (EMT) probably through TGF-β1 signaling [3].

In summary, Krt17 has diverse functions in different disease contexts. In cancer, it can influence tumor growth and response to immunotherapy. In fibrosis-related diseases, it promotes fibrotic processes. Mouse models, such as those used in colorectal cancer, liver fibrosis, and pulmonary fibrosis studies, have been crucial in revealing these functions of Krt17, providing insights into potential therapeutic strategies for these diseases.

References:

1. Liang, Wenfeng, Liu, Huashan, Zeng, Ziwei, Huang, Liang, Kang, Liang. . KRT17 Promotes T-lymphocyte Infiltration Through the YTHDF2-CXCL10 Axis in Colorectal Cancer. In Cancer immunology research, 11, 875-894. doi:10.1158/2326-6066.CIR-22-0814. https://pubmed.ncbi.nlm.nih.gov/37129929/

2. Jaeger, Benedikt, Schupp, Jonas Christian, Plappert, Linda, Kaminski, Naftali, Prasse, Antje. 2022. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. In Nature communications, 13, 5637. doi:10.1038/s41467-022-33193-0. https://pubmed.ncbi.nlm.nih.gov/36163190/

3. Chen, Jing, Ge, Si-Jia, Feng, Hai-Juan, Huang, Wei, Lu, Cui-Hua. 2021. KRT17 Promotes the Activation of HSCs via EMT in Liver Fibrosis. In Journal of clinical and translational hepatology, 10, 207-218. doi:10.14218/JCTH.2021.00101. https://pubmed.ncbi.nlm.nih.gov/35528988/

4. Tang, Shasha, Liu, Wenjing, Yong, Liyun, Wang, Hui, Cai, Fengfeng. 2022. Reduced Expression of KRT17 Predicts Poor Prognosis in HER2high Breast Cancer. In Biomolecules, 12, . doi:10.3390/biom12091183. https://pubmed.ncbi.nlm.nih.gov/36139022/