KRT19

What is KRT19 protein?

KRT19 gene (keratin 19) is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q21. The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. Unlike its related family members, this smallest known acidic cytokeratin is not paired with a basic cytokeratin in epithelial cells. It is specifically expressed in the periderm, the transiently superficial layer that envelopes the developing epidermis. The KRT19 protein is consisted of 400 amino acids and KRT19 molecular weight is approximately 44.1 kDa.

What is the function of KRT19 protein?

KRT19 protein is an intermediate filament protein expressed in epithelial cells that plays a role in a variety of biological processes, including maintaining the integrity of cell structure, regulating cell signaling, and participating in cell migration and proliferation. In cancer research, KRT19 has received particular attention as a biomarker for breast cancer and other epithelial tumors. The level of KRT19 expression may vary in different types of breast cancer and is strongly associated with tumor aggressiveness and prognosis. In addition, KRT19 is involved in the regulation of the NOTCH signaling pathway, influencing tumor cell proliferation, migration, invasion, drug resistance, and globular formation through interaction with the β-catenin/RAC1 complex. In breast cancer stem cells, downregulation of KRT19 expression is associated with enhanced stem properties of the tumor.

Fig1. Schematic diagram demonstrating the KRT19-mediated modulation of cancer reprogramming. (Subbroto Kumar Saha, 2018)

KRT19 related signaling pathway

KRT19 protein is an intermediate filament protein that plays a role in a variety of biological processes, especially in cancer research, where it is closely related to the occurrence, development and treatment response of tumors. In breast cancer, KRT19 expression is strongly associated with tumor aggressiveness and prognosis, and increased expression levels are associated with poor clinical outcomes. KRT19 regulates the NUMB dependent NOTCH signaling pathway by interacting with the β-catenin/RAC1 complex and influences the properties of breast cancer cells. In addition, KRT19 is involved in regulating the expression of cell cycle-related genes, including interactions with cyclin D3, a cell cycle regulator, affecting cell cycle progression and cancer cell sensitivity to CDK inhibitors.

KRT19 related diseases

KRT19 protein, a member of the keratin family, is mainly expressed in epithelial cells and plays an important role in maintaining the integrity of cell structure. In cancer research, KRT19 is commonly used as a tumor marker, especially in the diagnosis and prognosis assessment of breast, liver, and ovarian cancers. KRT19 is closely related to the proliferation, migration, invasion, drug resistance and globular formation of tumor cells. Studies have shown that KRT19 can regulate NUMB expression in the NOTCH signaling pathway by interacting with the β-catenin/RAC1 complex, thereby affecting the characteristics of tumor cells. The down-regulation of KRT19 expression may lead to the activation of NOTCH signaling pathway, thus promoting the proliferation and invasion of tumor cells.

Bioapplications of KRT19

KRT19 is an intermediate filament protein that is commonly expressed in epithelial cells and plays a role in a variety of biological processes. In medical research and clinical applications, KRT19 is primarily used as a biomarker for a variety of tumors, including breast, lung, liver, and ovarian cancers. The expression level of KRT19 is closely related to the aggressiveness, prognosis and treatment response of the tumor. In breast cancer, KRT19 is associated with dryness, metastasis, and drug resistance of tumor cells. In liver cancer, KRT19 has been found to enter the nucleus and promote liver cancer by interacting with histone deacetylase. In addition, KRT19 is a potential molecular marker in lung cancer that is associated with tumor progression and overall patient survival.

Case Study 1: Zhikai Wang, 2022

Cancer immunotherapies often do not work well because most cancer cells have few T cells inside them, suggesting that cancer cells are able to suppress T cell penetration. This study shows that human pancreatic ductal adenocarcinoma, colorectal cancer, and breast cancer cells are coated with transglutaminase-2 (TGM2) -dependent covalent CXCl12-keratin 19 (KRT19) heterodimers that form a filamentous network. Since the dimeric form of CXCL12 inhibits the activity of human T cells, researchers further explored whether this polymerized CXCL12-KRT19 coating mediates T cell exclusion. Mouse tumors containing control PDA cells showed a coating of CXCL12-KRT19, rejected T cells, and did not respond to anti-PD-1 antibody therapy. Tumors that do not contain KRT19 or TGM2-expressing PDA cells do not have CXCL12-KRT19 coatings, are permeable by activated CD8+ T cells, and their growth is inhibited by anti-PD-1 antibody treatment. Therefore, cancer cells evade cancer immune attack by assembling the CXCL12-KRT19 coating.

Fig1. The interactions of CXCL12 and KRT19.

Fig2. Sections of hepatic metastases formed with luciferase-expressing sgScramble control PDA cells, sgKRT19-edited cells were stained.

Case Study 2: Changsheng Zhou, 2023

Pancreatic cancer is a very aggressive disease with rapid progression and poor prognosis, which poses a serious threat to human health. Tumors that express keratin 19 (K19) are more aggressive and have a worse prognosis. However, the role of K19 in pancreatic cancer and its mechanisms remain unclear. This study examined the expression of K19 in pancreatic cancer tissue and evaluated its effects on pancreatic cancer cell proliferation, apoptosis, and metastasis, as well as its effect on the Hedgehog signaling pathway. The results showed that the expression of K19 was significantly up-regulated in pancreatic cancer, which could promote the proliferation and metastasis of cancer cells, inhibit apoptosis, and was associated with poor prognosis. These effects are mainly achieved by activating the Hedgehog signaling pathway.

Fig3. Knockdown of K19 inhibited the cell cycle progression of PANC-1 and MIA-PaCa-2 cells.

Fig4. Overexpression of K19 upregulated the expression of Gli1 in PANC-1 and MIA-PaCa-2 cells.

KRT19 has several biochemical functions, for example, structural molecule activity. Some of the functions are cooperated with other proteins, some of the functions could acted by KRT19 itself. We selected most functions KRT19 had, and list some proteins which have the same functions with KRT19. You can find most of the proteins on our site.

KRT19 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with KRT19 here. Most of them are supplied by our site. Hope this information will be useful for your research of KRT19.