DKK-1, human
- Known as:
- DKK-1, H. sapiens
- Catalog number:
- p705-25
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- 101bio
- Gene target:
- DKK-1 human
Related genes to: DKK-1, human
- Gene:
- DKK1 NIH gene
- Name:
- dickkopf WNT signaling pathway inhibitor 1
- Previous symbol:
- -
- Synonyms:
- SK, DKK-1
- Chromosome:
- 10q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-01
- Date modifiied:
- 2018-06-28
Related products to: DKK-1, human
Related articles to: DKK-1, human
- The expansion of immunosuppressive myeloid cells drives tumor progression, yet clinical strategies aimed at depleting these populations have shown limited effects and high toxicity. Because myeloid cells arise from hematopoietic progenitors, we asked whether solid tumors durably reprogram hematopoietic stem and progenitor cells (HSPCs) to sustain pathological myeloid bias. Here, we show treatment-naïve stage-III breast cancer (BC) patients and murine models of primary BC exhibited expansion of bone marrow HSPCs with enhanced myeloid output. Transplantation assays further demonstrated that tumor-educated HSPCs retained durable myeloid bias following transfer into healthy recipients and promoted tumor progression upon secondary challenge, accompanied by selective expansion of multi-potent progenitors (MPPs) and mature myeloid cells. In contrast, transplantation of long-term HSCs did not confer durable hematopoietic changes or enhanced tumor growth, indicating that tumor-induced myeloid bias is mediated by downstream progenitors. Consistently, depletion of mature myeloid cells did not alter HSCs but triggered rapid MPP expansion and myeloid rebound in tumor-bearing mice compared to no-tumor controls. Among progenitor subsets, MPP3s emerged as the principal drivers of tumor-associated myelopoiesis. Single-cell RNA sequencing of BC patient bone marrow revealed reduced Wnt-β-catenin signaling in HSPCs and identified DKK1, a bone-derived Wnt inhibitor elevated during BC progression, as a mediator of MPP3 reprogramming. Targeting bone-derived DKK1 limited HSPC engraftment following transplantation into naïve mice, and reduced BC progression, MPP3 expansion, and myeloid output in tumor bearing mice. These findings highlight solid tumor-induced hematopoietic reprogramming and identify bone-derived DKK1 as a regulator of MPP3 fate. - Source: PubMed
Publication date: 2026/09/25
Eul EmilyFuresi GiuliaHan WentaoLee SeunghyunWatson MarkAft RebeccaChallen GrantFaccio Roberta - Multiple myeloma (MM) is a malignancy of plasma cells with complex pathogenesis and unmet clinical needs. ERP44 is an Endoplasmic Reticulum (ER)-resident protein involved in protein folding, but its role in MM remains unclear. Kaplan-Meier survival analysis showed that high ERP44 expression correlated with poor prognosis in MM patients, prompting us to investigate its biological function and regulatory mechanisms. Using lentiviral-mediated overexpression and knockdown strategies in MM cell lines, we demonstrated that ERP44 significantly promoted cell proliferation in vitro, and ERP44 knockdown suppressed tumor growth in a xenograft mouse model. Mechanistically, we identified USP32 as an upstream regulator that interacted with and stabilized ERP44 through deubiquitination. Functional rescue experiments showed that ERP44 overexpression partially reversed USP32 knockdown-induced proliferation inhibition, confirming that USP32 promoted MM cell proliferation through ERP44. RNA sequencing combined with Western blotting revealed that ERP44 activated the PI3K-AKT signaling pathway, leading to upregulation of CDK2 and Cyclin D1 and driving cell cycle progression. Notably, the PI3K-AKT inhibitor LY294002 significantly attenuated the proliferative advantage conferred by ERP44 overexpression, suggesting this pathway as a critical downstream effector. Furthermore, ERP44 overexpression upregulated UPR markers (GRP78, XBP1, and CHOP) as well as osteolytic factors (DKK1, RANKL, and MIP-1α), indicating its broader role in UPR and bone destruction. Collectively, these findings identify ERP44 as a pro-proliferative factor in MM and establish a USP32-ERP44-PI3K-AKT regulatory axis. - Source: PubMed
Publication date: 2026/09/24
Gao YujuanWang HongjiaSun JiayueMa Guibo - Osteosarcoma (OS) is an aggressive primary bone malignancy that predominantly affects children and adolescents. Although surgery and chemotherapy have improved survival, therapeutic progress has remained limited over recent decades. Aberrant fatty acid metabolism has been increasingly implicated in OS progression, yet its distribution across different cellular compartments of the tumor microenvironment remains unclear. In this study, we integrated single-cell RNA-sequencing data from 140,562 cells across 17 OS patients and characterized the metabolic heterogeneity of tumor microenvironment. Two fatty acid metabolism-associated populations were identified: IBSP+ malignant osteosarcoma cells and SPARC+ macrophages. IBSP+ malignant cells showed preferential activation of fatty acid degradation and occupied an intermediate state along the pseudo-time trajectory. Lipid uptake and cholesterol efflux programs reached their highest activity near this state, indicating substantial lipid metabolic remodeling along the inferred transition among malignant-cell states. By contrast, SPARC macrophages exhibited a lipid-adapted, immunosuppressive phenotype accompanied by elevated fatty acid degradation activity. Cell-cell communication analysis further identified IBSP malignant cells as a major source of APOE- and SPP1-related signals directed toward SPARC+ macrophages, suggesting coordinated metabolic communication between these populations. To evaluate its clinical relevance, we applied transcriptomic deconvolution to independent OS cohorts. Concurrent enrichment of IBSP+ malignant cells and SPARC+ macrophages was associated with significantly shorter overall survival. Comparison of the double-high and double-low groups subsequently identified DKK1 as a candidate effector linked to this adverse metabolic niche. Consistent with this observation, DKK1 silencing in MG-63 cells reduced proliferation, colony formation, migration, and invasion. Collectively, these findings characterize fatty acid metabolism-associated cellular heterogeneity and a clinically relevant association between IBSP malignant cells and SPARC macrophages in OS, while identifying DKK1 as a candidate prognostic and therapeutic factor associated with the double-high phenotype. - Source: PubMed
Publication date: 2026/09/07
Wang LifangGao MeiyanLiang Zhizhong - Osteoporosis is characterized by reduced bone mineral density (BMD) and an increased risk of fractures, but the relationships between plasma proteins and site-specific BMD phenotypes remain unclear. We aimed to investigate the potential causal associations of plasma proteins on BMD using a Mendelian randomization (MR). - Source: PubMed
Publication date: 2026/09/21
Lv KuiFang JialiuWang ShengyouXing XingZhu Rui - Immune checkpoint blockade has transformed treatment in selected gastrointestinal (GI) cancers, yet primary resistance, incomplete responses and acquired resistance remain common. This heterogeneity is not explained by tumour-cell genomics alone; extracellular signalling programmes within the tumour microenvironment can determine immune recruitment, access and adaptation to therapy. The tumour secretome-including cytokines, chemokines, growth factors, complement components, matricellular proteins, soluble checkpoint molecules and extracellular-vesicle-associated cargo-regulates immune-cell recruitment, exclusion, suppression, tertiary lymphoid structure formation and exhaustion across anatomical and molecular contexts. Across gastric and esophageal cancers, colorectal cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma and biliary tract cancers, recurrent suppressive circuits include TGF-β, VEGF, CXCL12-CXCR4, CXCL8/IL-8-CXCR1/2, CCL2-CCR2, CSF1-CSF1R, IL-6-family cytokines, SPP1/osteopontin, periostin, galectins, DKK1, MIF, complement and soluble or vesicular PD-L1. Conversely, CXCL9/10/11-CXCR3 signalling and CXCL13-associated tertiary lymphoid structures characterise immune-permissive states that can support checkpoint responsiveness. We organise these circuits into four overlapping functional modules-myeloid-enriched, fibroblast-driven exclusion, angiogenic-immunosuppressive and immune-permissive-and apply a four-level evidence hierarchy that separates clinical validation from mechanistic inference. Clinically useful secretome biomarkers will therefore need to integrate cellular source, spatial localisation, receptor context, temporal dynamics and linkage to actionable immune-state transitions. - Source: PubMed
Publication date: 2026/09/11
Li KexunQian ZilongMao JieHan YongtaoLeng Xuefeng