Ask about this productRelated genes to: CD133 antibody
- Gene:
- PROM1 NIH gene
- Name:
- prominin 1
- Previous symbol:
- PROML1, MCDR2, STGD4
- Synonyms:
- AC133, CD133, RP41, CORD12
- Chromosome:
- 4p15.32
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-15
- Date modifiied:
- 2016-10-05
Related products to: CD133 antibody
Related articles to: CD133 antibody
- The human PROMININ-1 (PROM-1, CD133), detected by its AC133 epitope, is expressed on the surface of leukemia-initiating cells of Philadelphia chromosome-positive (Ph+) leukemia cells. Ninety-five percent of chronic myeloid leukemia (CML) cases are Ph+. Ph+ acute lymphoblastic leukemia (ALL) accounts for twenty-five to thirty percent of adult ALL and is considered a high-risk ALL subgroup. Targeting the t(9;22)-fusion protein BCR::ABL1 with ABL1-directed kinase inhibitors (TKIs) is a proven therapeutic concept for CML and Ph+ ALL. Resistance against TKI comprises mutations in BCR::ABL1, but many patients exhibit a primary resistance with unknown mechanisms. Here, we investigated the impact of PROM-1 on the leukemogenesis and the therapy response of Ph+ leukemias. We applied flow cytometry, co-immunoprecipitation, immunoblotting, stem cell assays, and leukemia induction in vivo to cell lines, syngeneic mouse models, and human Ph+ long-term cultures. We found a direct relationship between BCR::ABL1 and PROM-1, a shift from CML towards ALL upon the loss of Prom-1, as well as a link between the response to TKIs and the PROM-1 expression. In contrast to solid tumors, resistance was accompanied by a progressive loss of PROM-1. Our data suggest that PROM-1 plays an essential role in both cell fate decision and induction of the BCR::ABL1-related leukemic phenotype, highlighting its impact on the drug response of Ph+ leukemias. Teaser abstract The Philadelphia chromosome (Ph) is the product of the t(9;22), which fuses the BCR gene on chromosome 22 to the ABL1 gene on chromosome 9. The result is the BCR::ABL1 oncogene, which is responsible for the induction of chronic myeloid leukemia (CML) and for about a third of acute lymphoblastic leukemia (Ph+ ALL). Only little is known about how t(9;22) induces either CML or ALL, and why there is a difference between the two diseases regarding their response to inhibitors that can inactivate BCR::ABL1. Here, we show that a gene called PROMININ-1 is involved in both processes: determining whether BCR::ABL1 induces CML or ALL, and explaining the weaker response of Ph+ ALL compared to CML to inhibitors of BCR::ABL1. We found that the reduction of PROMININ-1 increased the proportion of ALL induced by BCR::ABL1 in the mouse. We could not reproduce these findings in humans but distinguish CML from Ph+ ALL by the expression of PROMININ-1. Also resistance to BCR::ABL1 inhibitors was associated with low expression of PROMININ-1 in Ph+ ALL. These findings are in contrast to observations in solid tumors where a higher level of PROMININ-1 is accompanied by therapy resistance. Our findings contribute to a better understanding of the different types of Ph+ leukemia and their response to therapy, which will help patients better manage these diseases. - Source: PubMed
Publication date: 2026/10/06
Metodieva AnnaKarbanová JanaChiriches ClaudiaMian Afsar AliCarmeliet PeterTjwa MarcCorbeil DenisRuthardt Martin - Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits high metastatic potential, linked not only to intrinsic cancer cell traits but also to critical crosstalk with the tumor microenvironment. However, the coevolutionary mechanisms between cancer cells and multiple stromal subpopulations in driving distant metastasis remain poorly understood. Therefore, this study aimed to explore the microenvironmental regulatory mechanisms of breast tumor-initiating cells and their roles in HER2-positive breast cancer metastasis. Integrated multi-omics analyses (spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics) were used to identify novel cell subpopulations and their interactions. High-throughput sequencing of exosomal microRNAs (miRNAs) and single-nucleus RNA from the same tissue was performed to explore the molecular mechanisms underlying cell crosstalk. In vitro experiments were conducted to verify the interaction between stromal cells and prominin 1 (PROM1) SMAD family member 5 (SMAD5) cells. In vivo murine breast cancer models were established to confirm the role of stromal subpopulations in pulmonary metastasis, and parabiosis assays were carried out to compare key cell subpopulations between tumor-bearing mice and normal mice. Clinical samples were analyzed to correlate key cell subpopulations with clinicopathological features and prognosis. A breast tumor-initiating subpopulation, PROM1 SMAD5 cells, and its interactions with stromal cells, specifically adiponectin (ADIPOQ) notch receptor 4 (NOTCH4) adipocytes and decorin (DCN) transmembrane 4 L six family member 1 (TM4SF1) fibroblasts, were identified by integrated multi-omics analyses. Mechanistically, these 2 stromal subpopulations delivered functional miRNAs and mediated coatomer protein complex subunit alpha (COPA)-dependent epidermal growth factor receptor (EGFR) activation in PROM1SMAD5 cells, thereby triggering the EGFR-SMAD5-cytochrome P450 family 3 subfamily A member 4 (CYP3A4) axis to induce partial epithelial-mesenchymal transition (pEMT) and metastasis. Additionally, stroma-secreted exosomal miR-671-3p down-regulated Claudin1 in PROM1SMAD5 cells, promoting their evolution into PROM1SMAD5Claudin1 subpopulations with enhanced stemness and metastatic potential. In vivo experiments confirmed that the 2 stromal subpopulations markedly promoted pulmonary metastasis, and the 3 identified subpopulations preferentially accumulated in the primary tumors, lymph nodes, and pulmonary metastatic lesions of tumor-bearing mice. Clinically, these 3 subpopulations form a "trinity niche", whose aggregation associated with HER2 positivity, high malignancy, and lymph node/pulmonary metastasis, and predicted poor prognosis. This study clarified the microenvironmental regulation of breast tumor-initiating cells and provided new insights into precision therapy. - Source: PubMed
Publication date: 2026/09/09
Yin HuijingWang WeiGe JingFan GuangjianShi JichaoTian YeKong DepingZhang FanyiWei JingZhan HongruiXu ZhenyuGe JintongWang ShuweiZhang ZhimingZheng YunnaZhu ZhifaZi QingzhenYao XiaohuaDing YantingSong BoLi RuizhiFan LimingYin HaoJiang YinghaoZhang ShaoqianFu XingningWang JingZhou YanXue HaihuaQiu YannanGe LingYang YuqinJin YinhuiLou BinbinDing ShuningZhang TaoWei DenghuiZhu Li - Obesity is a major risk factor for colorectal cancer (CRC), promoting tumor initiation through chronic inflammation and metabolic dysregulation. Cancer stem cells (CSCs) drive CRC progression through Notch1, Wnt/β-catenin (Wnt), and PI3K/mTOR (mTOR) signaling. Omega-3 polyunsaturated fatty acids (EPA and DHA) and epigallocatechin-3-gallate (EGCG) may modulate these pathways. This study investigated the effects of obesogenic-like stimuli on CSC-related CRC signaling and the preventive potential of EPA:DHA-EGCG in patient-derived organoids (PDOs) from normal mucosa (NM) of non-obese (non-OB) patients. CD133 and CD44 expression was evaluated in tumor tissues and matched NM from obese (OB) and non-OB CRC patients. PDOs derived from NM of non-OB patients were exposed to an adipocyte-conditioned medium reproducing an obesogenic adipokine profile, with or without EPA:DHA (1:1) plus EGCG (EDE). Viability, morphology, and molecular markers of stemness, differentiation, and CRC-related pathways were assessed. OB CRC tissues exhibited a CSC change from CD133-high/CD44-low to CD44-high/CD133-low compared with non-OB CRC. In PDOs, OB-EDE recapitulated this CD44-high/CD133-low phenotype, increasing organoid viability and size while maintaining KRT20 comparable to control (CTRL). HES1 was significantly upregulated, consistent with modulation of Notch1 signaling. OB-EDE downregulated Wnt target genes and increased the mTOR downstream effector p-S6R. OB + EDE exerted marker- and pathway-specific effects, maintaining PROM1 at CTRL levels, reducing CD44 and HES1, and increasing KRT20, while LGR5 remained suppressed. Compared with OB-EDE, OB + EDE further reduced the expression of Wnt target genes and reduced p-S6R to CTRL, whereas p-mTOR/mTOR was not significantly affected. Overall, obesogenic-like stimuli were associated with a CD44-high stem-like phenotype accompanied by coordinated changes in Notch1, Wnt and mTOR signaling. EDE exerted differential effects on these molecular alterations, supporting its potential as a complementary bioactive strategy in obesity-associated CRC. Pharmacological inhibition using DAPT provided preliminary functional support for a contribution of Notch1 signaling to the maintenance of this obesogenic phenotype. - Source: PubMed
Publication date: 2026/09/02
Calafato GiuliaBernardi AliceAlquati ChiaraCuicchi DajanaButtitta FrancescoDi Paola Floriana JessicaPierantoni ChiaraCeccarelli ClaudioPariali MilenaPiazzi GiuliaRicciardiello Luigi - To describe the genetic resolution rate, molecular findings, and genotype-phenotype correlations of non- and non- inherited macular dystrophies (IMDs) within an Irish inherited retinal disease (IRD) registry. - Source: PubMed
Publication date: 2026/08/20
Harford DeirdreConway MarcusMoran BridgetZhu JuliaTurner JacquelineDockery AdrianO'Byrne James JFlitcroft D IanBurke TomásStephenson Kirk A JFarrar G JaneKeegan David J - Vasculogenic mimicry (VM), characterized by the de novo formation of microvascular-like channels derived from aggressive tumor cells without involving traditional endothelial cells, is a pivotal pathological hallmark driving extreme invasiveness and dismal prognosis in hepatocellular carcinoma (HCC). This study aimed to establish a VM-based molecular subtyping system and systematically characterize its associated biological features, thereby providing a potential framework for individualized prognostic assessment and treatment decision-making in HCC. We integrated curated VM-associated gene sets with single-cell RNA sequencing data to identify malignant epithelial cell-enriched VM-associated candidate genes. Subsequently, univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression were sequentially performed to identify six prognostic VM-related genes: , , , , , and . HCC patients were stratified into VM, Mixed-VM, and Non-VM subtypes according to VM scores. Kaplan-Meier survival analysis, time-dependent ROC analysis, and Cox regression were used to assess prognostic performance. The biological features of the classification system were evaluated using bulk transcriptomic cohorts, spatial transcriptomics, Cytometry by Time-of-Flight (CyTOF), metabolomics, lipidomics, somatic mutation and copy number alteration analyses, and treatment-related HCC cohorts. The VM score-based classification stratified HCC patients into three molecular subtypes with distinct prognostic and biological characteristics. Patients classified as the VM subtype had significantly poorer overall survival than those classified as Mixed-VM or Non-VM subtypes, and this prognostic pattern was validated across independent cohorts. Multi-omics analyses showed that the VM subtype was associated with YAP-TAZ-TEAD-related transcriptional programs, stemness/proliferation-related features, immunoregulatory and exhaustion-like tumor microenvironmental characteristics, and distinct metabolic and lipidomic alterations involving modified nucleosides, keto acid-related metabolites, cholesteryl esters, and sphingolipid-related species. Spatial transcriptomics revealed focal enrichment of VM-score-high regions and their association with YAP-TAZ-TEAD and immune checkpoint-related signatures. In orthotopic HCC mouse models, YAP1 overexpression increased PAS/CD34 VM-like structures, whereas verteporfin treatment reduced these structures. In two treatment-related cohorts, the Non-VM subtype showed higher response rates to sorafenib and transarterial chemoembolization (TACE) than the VM subtype. Connectivity Map (CMap)-based computational drug prioritization and molecular docking analysis prioritized ivermectin as a candidate compound; however, its antitumor activity requires further experimental validation. This study establishes a VM score-based molecular classification framework for HCC and identifies VM-subtype-associated prognostic, spatial, immune, metabolic, genomic, and therapeutic features. These findings provide a candidate framework for molecular risk stratification and subtype-guided therapeutic exploration in HCC. - Source: PubMed
Publication date: 2026/08/02
Tao YutingLiao ShuzhenLiu TaoLai RuyiFeng ChaoWang Qiuyan