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KRT19, classified as a type I acidic cytokeratin, serves as a crucial intermediate filament protein in maintaining the structural integrity of epithelial cells [1]. Its significance extends notably to various cancer types. For example, fragments of soluble KRT19 protein are detectable in the bloodstream of cancer patients, offering a means to monitor tumor load and disease progression in specific cancer types [2]. In cystic fibrosis, KRT19 influences CFTR function by bolstering its presence at the cell membrane and enhancing its density there, effectively impeding CFTR internalization [3].
Furthermore, KRT19 is implicated in driving tumorigenesis, tumor invasion, and metastasis by interacting with proteins like Ki-67 in lung squamous cancer [4]. Conversely, it exhibits tumor-suppressive properties in breast cancer by modulating the nuclear translocation of EGR1 to the PTEN promoter [5]. Moreover, KRT19 serves as a prognostic marker and plays distinct biological roles in various cancers, including hepatocellular carcinoma and pancreatic neuroendocrine tumors [6]. It is also employed as a marker for detecting disseminated tumor cells in breast cancer patients' lymph nodes, peripheral blood, and bone marrow, offering prognostic insights [7]. Its involvement extends to regulating the nuclear import of early growth response-1 in breast cancer cells, thereby influencing cell proliferation and migration [8].
Additionally, KRT19 interacts directly with the β-catenin/RAC1 complex to modulate the NUMB-dependent NOTCH signaling pathway and breast cancer characteristics [9]. Nonetheless, the precise role of KRT19 in cancer progression—whether it promotes or suppresses it—requires further elucidation through extensive molecular investigations [10]. Notably, KRT19 is associated with hepatocellular carcinoma malignancy, where it enhances Notch1 signaling and fosters cancer malignancy [11]. Its expression or expression-related signatures are emerging as predictors of HCC recurrence and survival post-liver transplantation [12]. In the realm of atopic eczema, KRT19's correlation with its development underscores its potential role in this condition [13].
References:
[1] J. Gisby, C. Clarke, N. Medjeral-Thomas, T. Malik, A. Papadaki, P. Mortimeret al., "Longitudinal proteomic profiling of dialysis patients with covid-19 reveals markers of severity and predictors of death",, 2020. https://doi.org/10.1101/2020.11.05.20223289
[2] P. Wang, V. Magdolen, C. Seidl, J. Dorn, E. Drecoll, M. Kotzschet al., "Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer", British Journal of Cancer, vol. 119, no. 7, p. 1-9, 2018. https://doi.org/10.1038/s41416-018-0260-1
[3] F. Gisler, T. Känel, R. Kraemer, A. Schaller, & S. Gallati, "Identification of snps in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis", European Journal of Human Genetics, vol. 21, no. 4, p. 397-403, 2012. https://doi.org/10.1038/ejhg.2012.181
[4] M. Yi, B. Dong, Q. Chu, & K. Wu, "Prognostic significance of krt19 in lung squamous cancer", Journal of Cancer, vol. 12, no. 4, p. 1240-1248, 2021. https://doi.org/10.7150/jca.51179
[5] S. Saha, K. Kim, G. Yang, H. Choi, & S. Cho, "Cytokeratin 19 (krt19) has a role in the reprogramming of cancer stem cell-like cells to less aggressive and more drug-sensitive cells", International Journal of Molecular Sciences, vol. 19, no. 5, p. 1423, 2018. https://doi.org/10.3390/ijms19051423
[6] X. Wang, X. Xu, P. Chen, Y. Qin, T. Gao, J. Jinget al., "Brafv600e‑induced krt19 expression in thyroid cancer promotes lymph node metastasis via emt", Oncology Letters, 2019. https://doi.org/10.3892/ol.2019.10360
[7] L. Mi, N. Liang, & H. Sun, "A comprehensive analysis of krt19 combined with immune infiltration to predict breast cancer prognosis", Genes, vol. 13, no. 10, p. 1838, 2022. https://doi.org/10.3390/genes13101838
[8] J. Ju, S. Oh, K. Lee, W. Yang, K. Nam, H. Moonet al., "Cytokeratin19 induced by her2/erk binds and stabilizes her2 on cell membranes", Cell Death and Differentiation, vol. 22, no. 4, p. 665-676, 2014. https://doi.org/10.1038/cdd.2014.155
[9] J. Ju, W. Yang, K. Lee, S. Oh, K. Nam, S. Shimet al., "Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells", Clinical Cancer Research, vol. 19, no. 16, p. 4335-4346, 2013. https://doi.org/10.1158/1078-0432.ccr-12-3295
[10] S. Saha, H. Choi, K. Bw, D. Aa, G. Yang, K. Kset al., "Krt19 directly interacts with β-catenin/rac1 complex to regulate numb-dependent notch signaling pathway and breast cancer properties", Oncogene, vol. 36, no. 3, p. 332-349, 2016. https://doi.org/10.1038/onc.2016.221
[11] X. Zhang, X. Xu, Z. Zhang, C. Xue, Z. Kong, S. Wuet al., "Linc-kilh potentiates notch1 signaling through inhibiting krt19 phosphorylation and promotes the malignancy of hepatocellular carcinoma", International Journal of Biological Sciences, vol. 17, no. 3, p. 768-780, 2021. https://doi.org/10.7150/ijbs.52279
[12] H. Rhee, H. Kim, J. Choi, H. Woo, J. Yoo, J. Nahmet al., "Keratin 19 expression in hepatocellular carcinoma is regulated by fibroblast-derived hgf via a met-erk1/2-ap1 and sp1 axis", Cancer Research, vol. 78, no. 7, p. 1619-1631, 2018. https://doi.org/10.1158/0008-5472.can-17-0988
[13] J. Frowein, P. Pagel, R. Kappler, D. Schweinitz, A. Roscher, & I. Schmid, "Microrna-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma", Hepatology, vol. 53, no. 3, p. 833-842, 2011. https://doi.org/10.1002/hep.24125
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