KCTD4 Human
Description
Association with Metastasis and Survival
-
Expression Patterns: KCTD4 is significantly upregulated in metastatic ESCC tissues compared to primary tumors (P < 0.05) . A tissue microarray (TMA) analysis of 180 ESCC patients revealed elevated KCTD4 levels in 47.8% of tumors versus matched normal tissues .
-
Prognostic Impact: High KCTD4 expression correlates with poor survival (13.0 vs. 37.0 months in low-expression cohorts) and advanced lymph node metastasis (N1/N2/N3 stages, P = 0.004) .
| Clinical Variable | Low KCTD4 (n=91) | High KCTD4 (n=89) | P Value |
|---|---|---|---|
| Lymph Node Metastasis | 42% | 67% | 0.004** |
| Distant Metastasis (M1) | 0% | 3.4% | 0.03* |
| 5-Year Survival Rate | 32% | 12% | <0.001*** |
Functional Role in Metastasis
-
In Vitro/In Vivo Models: Overexpression of KCTD4 in KYSE150 and KYSE410 cells increased invasion by 2.5–3.0-fold (Boyden chamber assay) and enhanced lymph node/lung metastasis in mouse models .
-
Epithelial-Mesenchymal Transition (EMT): KCTD4 upregulates fibronectin and suppresses E-cadherin, driving EMT .
Calcium Homeostasis Disruption
-
CLIC1 Interaction: KCTD4 binds to chloride intracellular channel protein 1 (CLIC1), disrupting its dimerization and increasing intracellular Cl⁻ levels. This activates L-type Ca²⁺ channels (LTCCs), elevating cytosolic Ca²⁺ .
-
Downstream Signaling: Elevated Ca²⁺ triggers NFATc1 nuclear translocation, inducing fibronectin transcription. Secreted fibronectin activates fibroblasts via α-SMA/FAP upregulation, creating a pro-metastatic TME through MMP24-mediated feedback .
Key Molecular Interactions
Lead Compound K279-0738
-
Mechanism: Inhibits KCTD4-CLIC1 interaction, reducing Ca²⁺ flux and fibronectin secretion .
-
Efficacy: In mouse models, K279-0738 suppressed lung metastasis by 70% without notable toxicity .
Future Directions
Product Specs
Product Science Overview
KCTD4 is a protein-coding gene that produces a protein involved in various cellular processes. The human recombinant version of KCTD4 is produced in E. coli as a single, non-glycosylated polypeptide chain containing 282 amino acids, with a molecular mass of 32.4 kDa . This recombinant protein is fused to a 23 amino acid His-tag at the N-terminus and is purified using proprietary chromatographic techniques .
The KCTD4 protein contains a BTB/POZ domain, which is known for its role in protein-protein interactions and transcriptional regulation through the control of chromatin structure and function . The BTB domain is involved in homodimerization, which is essential for the protein’s function .
The recombinant human KCTD4 protein is used in various research applications, including studies on protein-protein interactions, transcriptional regulation, and potassium channel function. It is also used in the development of assays and as a tool for understanding the molecular mechanisms underlying various diseases.
