Krt15, a type I keratin lacking a defined type II partner, plays a key role in maintaining cytoplasmic stability. It has been associated with various biological processes and disease conditions. In the context of some tissues, it may mark stem or progenitor cells, and is involved in processes like cell migration, invasion, and differentiation [2,5,6,8].

In colorectal cancer, KRT15 acts as an oncogene. Ectopic expression of KRT15 promotes cell migration and invasion, while silencing it suppresses these processes. This occurs at least partly through the β -catenin/MMP-7 signaling pathway, suggesting it as a potential therapeutic target for metastatic colorectal cancer [1].

In breast cancer, its role seems to be context-dependent. In invasive breast carcinoma, low KRT15 expression is associated with poor prognosis, and high expression is linked to immune-cell infiltration [4]. In early breast cancer screening, KRT15 assessment may be helpful, as it shows different correlations with clinical characteristics among different breast cancer subtypes [3].

In the lung, Krt15 protects against cigarette smoke-induced epithelial mesenchymal transformation by regulating MMP-9 expression, and Krt15+ cells can transform into alveolar type II cells to protect alveoli, suggesting it as a potential therapeutic target for COPD [7].

In the intestine, Krt15 labels long-lived, multipotent, and radio-resistant crypt cells, and loss of the tumor suppressor Apc in Krt15+ cells leads to adenoma and adenocarcinoma formation [8].

In conclusion, Krt15 has diverse functions in maintaining cellular stability, differentiation, and tissue homeostasis. Its role in cancer progression, especially in colorectal, breast, and intestinal cancers, and in lung diseases like COPD, is significant. Gene knockout and other functional studies in mouse models have been crucial in revealing these roles, providing insights into potential therapeutic strategies for these diseases.

References:

1. Chen, Weida, Miao, Chengli. 2022. KRT15 promotes colorectal cancer cell migration and invasion through β-catenin/MMP-7 signaling pathway. In Medical oncology (Northwood, London, England), 39, 68. doi:10.1007/s12032-021-01619-2. https://pubmed.ncbi.nlm.nih.gov/35477819/

2. Rao, X, Wang, J, Song, H M, Deng, B, Li, J G. 2019. KRT15 overexpression predicts poor prognosis in colorectal cancer. In Neoplasma, 67, 410-414. doi:10.4149/neo_2019_190531N475. https://pubmed.ncbi.nlm.nih.gov/31884802/

3. Zhang, Zijing, Wang, Hongying, Jin, Yiting, Zou, Liping, Zou, Qiang. 2023. KRT15 in early breast cancer screening and correlation with HER2 positivity, pathological grade and N stage. In Biomarkers in medicine, 17, 553-562. doi:10.2217/bmm-2023-0130. https://pubmed.ncbi.nlm.nih.gov/37814985/

4. Zhong, Pengcheng, Shu, Rong, Wu, Huiwen, Shen, Xiaoling, Hu, Yingjie. 2021. Low KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma. In Experimental and therapeutic medicine, 21, 305. doi:10.3892/etm.2021.9736. https://pubmed.ncbi.nlm.nih.gov/33717248/

5. Busslinger, Georg A, Weusten, Bas L A, Bogte, Auke, Brosens, Lodewijk A A, Clevers, Hans. . Human gastrointestinal epithelia of the esophagus, stomach, and duodenum resolved at single-cell resolution. In Cell reports, 34, 108819. doi:10.1016/j.celrep.2021.108819. https://pubmed.ncbi.nlm.nih.gov/33691112/

6. Ievlev, Vitaly, Lynch, Thomas J, Freischlag, Kyle W, Engelhardt, John F, Parekh, Kalpaj R. 2023. Krt14 and Krt15 differentially regulate regenerative properties and differentiation potential of airway basal cells. In JCI insight, 8, . doi:10.1172/jci.insight.162041. https://pubmed.ncbi.nlm.nih.gov/36512409/

7. Zhu, Wensi, Han, Linxiao, Wu, Yuanyuan, Zhu, Qiaoliang, Zhou, Jian. 2023. Keratin 15 protects against cigarette smoke-induced epithelial mesenchymal transformation by MMP-9. In Respiratory research, 24, 297. doi:10.1186/s12931-023-02598-w. https://pubmed.ncbi.nlm.nih.gov/38007424/

8. Giroux, Véronique, Stephan, Julien, Chatterji, Priya, Hamilton, Kathryn E, Rustgi, Anil K. 2018. Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating. In Stem cell reports, 10, 1947-1958. doi:10.1016/j.stemcr.2018.04.022. https://pubmed.ncbi.nlm.nih.gov/29805107/