Ask about this productRelated genes to: PAGE4 Blocking Peptide
- Gene:
- PAGE4 NIH gene
- Name:
- PAGE family member 4
- Previous symbol:
- GAGEC1
- Synonyms:
- PAGE-4, CT16.7
- Chromosome:
- Xp11.23
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-15
- Date modifiied:
- 2015-11-18
Related products to: PAGE4 Blocking Peptide
Related articles to: PAGE4 Blocking Peptide
- Hepatoblastoma is a primary malignant liver tumor in children, thought to arise from abnormal liver development during the fetal period. Approximately 90 % of cases harbor activating mutations in CTNNB1, which encodes β-catenin, while other genetic mutations are rare. Recent studies have shown that CTNNB1 mutations are frequently accompanied by increased expression of the transcriptional coactivator YAP, which promotes cell proliferation and suppresses apoptosis. Based on these findings, we established a hepatoblastoma model by introducing constitutively active forms of CTNNB1 and YAP into human induced pluripotent stem cell (iPSC)-derived hepatoblasts. Cells transduced with both genes showed distinct morphological changes and upregulation of CTNNB1, YAP, and their downstream target genes. RNA-seq followed by Gene Set Enrichment Analysis (GSEA) revealed that the gene expression profile of these cells closely matches that of hepatoblastoma patients. Utilizing this model, we identified Prostate-Associated Gene 4 (PAGE4) as a novel candidate gene involved in hepatoblastoma progression. Furthermore, immunohistochemistry of hepatoblastoma specimens confirmed that PAGE4 is indeed expressed at higher levels compared to normal liver tissue. Functional analysis in hepatoblastoma cell lines demonstrated that PAGE4 plays a role in promoting cell proliferation and resistance to apoptosis. Since PAGE4 is a known cancer/testis antigen with tumor-specific expression, our findings highlight it as a novel and promising therapeutic target for hepatoblastoma, particularly in the context of cancer immunotherapy. - Source: PubMed
Publication date: 2025/10/16
Kawakita IsseiHonda ShoheiYamada YutaTanaka ShugoKatayama YukoShionoiri TakeshiIshii AsukaKurosu HiroyukiHamada KazuyaKumagai KentaroNakazono KensukeSaito RinoTerasaka ChihiroTakahashi RyoKawahara InsuAra MomokoIwasaki SariTanaka SatoshiNiida AtsushiHiyama EisoTaketomi AkinobuTaniguchi Koji - Cytotrophoblast (CTB) of the early gestation human placenta are bipotent progenitor epithelial cells, which can differentiate into invasive extravillous trophoblast (EVT) and multinucleated syncytiotrophoblast (STB). Trophoblast stem cells (TSC), derived from early first trimester placentae, have also been shown to be bipotential; however, their cell-of-origin has not been identified. In this study, we set out to probe the transcriptional diversity of early and late first trimester villous CTB (vCTB) and compare these to TSC. To this end, we performed single-cell RNA sequencing (scRNA-seq) on placental villous tissue from early (6-8 weeks) and late (12-14 weeks) first trimester placentae; we also evaluated CTB within basal (maternal) and chorionic (fetal) regions of early first trimester placenta, both by scRNA-seq and GeoMx-based spatial transcriptomics. Finally, we performed scRNA-seq on three TSC lines, derived from 6-8 week gestation placentae, as well as on early first trimester CTB at several timepoints during TSC derivation. We found notable distinctions within CTB clusters based on gestational age, further influenced by location near the basal or chorionic plates. We identified trophoblast states representing "initial state" vCTB ( CTB progenitors), as well as additional CTB subtypes, precursor STB, and precursor and mature EVT. CTB progenitors were enriched in early first trimester placentae at the basal plate; overall, basal plate CTB were biased toward EVT, and chorionic plate CTB toward STB, precursors. Clustering and trajectory inference analysis indicated that TSC were most like EVT precursor cells. In fact, vCTB lost their "initial state" markers, including PAGE4, as they transitioned to TSC during culture. This was confirmed by flow cytometric analysis of 6 different TSC lines, which showed uniform expression of proximal column markers ITGA2 and ITGA5. Additionally, we found that ITGA5 CTB could be plated in 2D, forming only EVT upon spontaneous differentiation, but failed to form self-renewing organoids; conversely, ITGA5 CTB could not be plated in 2D, but readily formed organoids. Our findings suggest that distinct CTB states exist in different regions of the placenta as early as six weeks gestation and that current TSC lines most closely resemble ITGA5 CTB, biased toward the EVT lineage. - Source: PubMed
Publication date: 2025/06/11
Morey RobertSoncin FrancescaKallol SampadaSah NirvayManalo ZoeBui TonySlamecka JaroslavCheung Virginia ChuPizzo DonRequena Daniela FChang Ching-WenFarah OmarKittle RyanLam KellyMeads MorganHorii MarikoFisch Kathleen MParast Mana M - Cancer-associated fibroblasts (CAFs), the central players in the tumor microenvironment (TME), can promote tumor progression and metastasis via various functions. However, the properties of CAFs in prostate cancer (PCa) have not been fully assessed. Therefore, we aimed to examine the CAF characteristics in PCa and construct a CAF-derived signature to predict PCa prognosis. CAFs were identified using single-cell RNA sequencing (scRNA-seq) data from 3 studies. We performed the FindAllMarkers function to extract CAF marker genes and constructed a signature to predict the biochemical relapse-free survival (bRFS) of PCa in the Cancer Genome Atlas (TCGA) cohort. Subsequently, different algorithms were applied to reveal the differences of the TME, immune infiltration, treatment responses in the high- and low-risk groups. Additionally, the CAF heterogeneity was assessed in PCa, which were confirmed by the functional enrichment analysis, gene set enrichment analysis (GSEA), and AUCell method. The scRNA-seq analysis identified a CAF cluster with 783 cells and determined 183 CAF marker genes. Cell-cell communication revealed extensive interactions between fibroblasts and immune cells. A CAF-related prognostic model, containing 7 genes (ASPN, AEBP1, ALDH1A1, BGN, COL1A1, PAGE4 and RASD1), was developed to predict bRFS and validated by 4 independent bulk RNA-seq cohorts. Moreover, the high-risk group of the signature score connected with an immunosuppressive TME, such as a higher level of M2 macrophages and lower levels of plasma cells and CD8+ T cells, and a reduced reaction rate for immunotherapy compared with low-risk group. After re-clustering CAFs via unsupervised clustering, we revealed 3 biologically distinct CAF subsets, namely myofibroblast-like CAFs (myCAFs), immune and inflammatory CAFs (iCAFs) and antigen-presenting CAFs (apCAFs). In conclusion, the CAF-derived signature, the first of its kind, can effectively predict PCa prognosis and serve as an indicator for immunotherapy. Furthermore, our study identified 3 CAF subpopulations with distinct functions in PCa. - Source: PubMed
Liu WenWang MiaomiaoWang MiaoLiu Ming - Benign prostatic hyperplasia (BPH) is a common disease in elderly men with uncertain molecular mechanism, and oxidative stress (OS) has also been found associated with BPH development. Recently, we found that prostate-associated gene 4 (PAGE4) was one of the most significantly changed differentially expressed genes (DEGs) in BPH, which can protect cells against stress stimulation. However, the exact role of PAGE4 in BPH remains unclear. This study is aimed at exploring the effect of PAGE4 in BPH under OS. Human prostate tissues and cultured WPMY-1 and PrPF cells were utilized. The expression and localization of PAGE4 were determined with qRT-PCR, Western blotting, and immunofluorescence staining. OS cell models induced with HO were treated with PAGE4 silencing or PAGE4 overexpression or inhibitor (N-acetyl-L-cysteine (NAC)) of OS. The proliferation activity, apoptosis, OS markers, and MAPK signaling pathways were detected by CCK-8 assay, flow cytometry analysis, and Western blotting. PAGE4 was shown to be upregulated in human hyperplastic prostate and mainly located in the stroma. Acute OS induced with HO increased PAGE4 expression (which was prevented by OS inhibitor), apoptosis, cell cycle arrest, and reactive oxygen species (ROS) accumulation in WPMY-1 and PrPF cells. siPAGE4 plus HO potentiated HO effect via reducing the p-ERK1/2 level and increasing p-JNK1/2 level. Consistently, overexpression of PAGE4 offset the effect of HO and partially reversed the PAGE4 silencing effect. However, knocking down and overexpression of PAGE4 alone determined no significant effects. Our novel data demonstrated that augmented PAGE4 promotes cell survival by activating p-ERK1/2 and decreases cell apoptosis by inhibiting p-JNK1/2 under the OS, which could contribute to the development of BPH. - Source: PubMed
Publication date: 2022/05/19
Li YanLiu JianminLiu DaoquanWang ZhenZhou YongyingYang ShuGuo FengYang LiangZhang Xinhua - Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure but exist as conformational ensembles. Because of their structural plasticity, they can interact with multiple partners. The protein interactions between IDPs and their partners form scale-free protein interaction networks (PINs) that facilitate information flow in the cell. Because of their plasticity, IDPs typically occupy hub positions in cellular PINs. Furthermore, their conformational dynamics and propensity for post-translational modifications contribute to "conformational" noise which is distinct from the well-recognized transcriptional noise. Therefore, upregulation of IDPs in response to a specific input, such as stress, contributes to increased noise and, hence, an increase in stochastic, "promiscuous" interactions. These interactions lead to activation of latent pathways or can induce "rewiring" of the PIN to yield an optimal output underscoring the critical role of IDPs in regulating information flow. We have used PAGE4, a highly intrinsically disordered stress-response protein as a paradigm. Employing a variety of experimental and computational techniques, we have elucidated the role of PAGE4 in phenotypic switching of prostate cancer cells at a systems level. These cumulative studies over the past decade provide a conceptual framework to better understand how IDP conformational dynamics and conformational noise might facilitate cellular decision-making. - Source: PubMed
Publication date: 2021/11/27
Kulkarni PrakashAchuthan SrisairamBhattacharya SupriyoJolly Mohit KumarKotnala SourabhLeite Vitor B PMohanty AtishOrban JohnRoy SusmitaRangarajan GovindanSalgia Ravi