CXCL14

Case study 1: Tsung-Ming Chang, 2023

Lung cancer is a malignant tumor with metastatic potential. Chemokine ligand 14 (CXCL14) has been reported to be associated with different cancer cell migration and invasion. However, few studies have explored the function of CXCL14 and its specific receptor in lung cancer metastasis. This study aims to determine the mechanism of CXCL14-promoted cancer metastasis. The expression of CXCL14, atypical chemokine receptor 2 (ACKR2), and epithelial mesenchymal transition (EMT) markers was evaluated by the public database of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), Western blot, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and immunofluorescence (IF). Migration and wound healing assays were used to observe the motility of cancer cells. overexpression of CXCL14 and ACKR2 was observed in lung cancer datasets, human lung tumor sections, and lung cancer cells. Furthermore, the migration of CXCL14-promoted lung cancer cells was determined in vitro and in vivo. In particular, ACKR2 knockdown abolished CXCL14-induced cancer cell motility. Additionally, ACKR2 was involved in CXCL14-triggered phospholipase Cβ3 (PLCβ3), protein kinase Cα (PKCα), and proto-oncogene c-Src signaling pathway and subsequently upregulated nuclear factor κB (NF-κB) transcription activity leading to EMT and migration of lung cancer cells.

Fig1. H1299 and A549 cells were treated with CXCL14 (1-30 ng/ml) for 24 h, cell viability was evaluated using a CCK-8 assay.

Fig2. H1299 cells were treated with CXCL14 (30 ng/ml) to detect the phosphorylation of IKKα, IκBα, and p65 by using Western blot.

Case study 2: Anupam Kumar, 2022

The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T-cell effector function in glioma. The researchers used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response. They then used patient-derived glioma cultures and an immunocompetent murine model for malignant glioma to analyze the ability of tumor-intrinsic factors to promote a CD8+ T-cell response. As compared with isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages, increased MHC class I expression, enrichment of genes associated with antigen presentation and processing, and increased tumor cell secretion of the chemokine CXCL14. CXCL14 promoted activated CD8+ T-cell chemotaxis in vitro.

Fig3. Increased expression of CXCL14 in RAF altered astrocytoma (n=38) versus RAF wildtype astrocytoma (n=164) in a cohort of pediatric low-grade and high-grade astrocytoma.

Fig4. Chemotaxis of activated CD8+ T cells toward increasing concentration of CXCL14 ligand (25-100ng/ml) by transwell migration assay.

Fig1. Schematic mechanism of CXCL14 promotes tumor metastasis in lung cancer. (Tsung-Ming Chang, 2023)

Fig2. Schematic diagram illustrating the mechanisms and therapeutic impact of hypoxic tumor microenvironment (HTM)-regulated CXC chemokine ligand 14 (CXCL14) in glioblastoma progression. (Sung-Tai Wei, 2023)

CXCL14 involved in several pathways and played different roles in them. We selected most pathways CXCL14 participated on our site, such as Cytokine-cytokine receptor interaction, Chemokine signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with CXCL14 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

CXCL14 has several biochemical functions, for example, chemokine activity, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CXCL14 itself. We selected most functions CXCL14 had, and list some proteins which have the same functions with CXCL14. You can find most of the proteins on our site.

CXCL14 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 CXCL14 here. Most of them are supplied by our site. Hope this information will be useful for your research of CXCL14.

TRIM23; TEX11; CXCR4; REL; nadA; q81t38_bacan