Ask about this productRelated genes to: PCDHGC3 antibody
- Gene:
- PCDHGC3 NIH gene
- Name:
- protocadherin gamma subfamily C, 3
- Previous symbol:
- PCDH2
- Synonyms:
- PC-43, PC43, PCDH-GAMMA-C3
- Chromosome:
- 5q31.3
- Locus Type:
- protocadherin
- Date approved:
- 2000-08-22
- Date modifiied:
- 2016-10-05
Related products to: PCDHGC3 antibody
Related articles to: PCDHGC3 antibody
- Brain metastases remain a major problem for cancer patients, impacting their treatment and survival. The pathogenesis of brain metastases is largely unknown. Recent reports indicate that the adhesion molecule protocadherin γ C3 (PCDHGC3) is differentially expressed in various cancer cells and endothelial cells of the blood-brain barrier (BBB), suggesting its involvement in the development of brain metastases. Therefore, we generated a PCDHGC3 knockout (KO) in the triple-negative breast cancer cell line HCC1806 and the malignant melanoma cell line A2058. Control and KO cells were compared using cell proliferation, adhesion and invasion assays, gene expression analyses and matrix metalloproteinase (MMP) activity assays. While the PCDHGC3 KO mutation led to increased proliferation in HCC1806 cells, with no difference observed in A2058, it significantly increased adhesion to in vitro BBB models as well as invasion in both HCC1806 and A2058 KO cell lines. Although changes in mRNA expression of genes involved in metastasis, angiogenesis and cell adhesion were found in PCDHGC3 KO breast cancer and melanoma cells, the number of genes with significantly increased mRNA expression was higher in A2058 KO cells than in HCC1806 KO cells. While the mRNA expression of MMP1 and 2 was increased in A2058 KO cells, no significant changes were found in HCC1806 KO cells. However, increased MMP activity in the cell culture medium was detected in HCC1806 KO cells, while A2058 KO cells showed lower MMP-activity compared to control. These findings provide insights into the role of PCDHGC3 in cancer cell extravasation during metastatic process and identify potential therapeutic targets for further investigation. - Source: PubMed
Publication date: 2026/04/18
Glogau PaulMi JunqiaoMeybohm PatrickBurek Malgorzata - Clear cell renal cell carcinoma (ccRCC) remains a major clinical challenge due to its high metastatic potential and limited treatment options. Here, we identified PCDHGC3 as a critical tumor suppressor, whose downregulation drives ccRCC aggressiveness. Through integrated molecular analyses, we demonstrated that PCDHGC3 deficiency promoted proliferation, epithelial-to-mesenchymal transition, and metastatic dissemination in both in vitro and in vivo models. Mechanistically, PCDHGC3 knockdown activated mTOR signaling, leading to aberrant HIF2α stabilization, a well-established oncogenic driver in ccRCC. Upstream of this cascade, PCDHGC3 loss was associated with increased focal adhesion kinase (FAK) activation, providing a context-specific link between membrane signaling and mTOR-HIF2α pathway activation. Pharmacological inhibition of mTOR suppresses HIF2α activity and targeting either pathway partially rescues the hyperproliferative and pro-metastatic phenotype of PCDHGC3-deficient cells. Proteomic analysis further revealed that PCDHGC3 loss reprograms lipid metabolism, particularly by increasing fatty acid synthesis and lipid droplet (LD) formation. We identify PLIN2, a HIF2α-regulated gene, as a key mediator of LD stability in PCDHGC3-knockdown cells. By sequestering lipids into LDs, PLIN2 protects against ferroptosis, an iron-dependent form of cell death triggered by lipid peroxidation. Notably, PLIN2 knockdown increases ferroptotic sensitivity, revealing LD biogenesis as a major survival mechanism in PCDHGC3-deficient ccRCC. Together, these findings establish a PCDHGC3-mTOR-HIF2α-PLIN2 axis that underlines both metastatic behavior and ferroptosis evasion. Clinically, this suggests that combining ferroptosis inducers with mTOR or HIF2α inhibitors-and potentially targeting PLIN2-could provide a multifaceted therapeutic strategy against advanced ccRCC. By elucidating the tumor-suppressive role of PCDHGC3, this study expands our understanding of clustered PCDH biology and offers novel insights for ccRCC management. - Source: PubMed
Publication date: 2026/03/26
Celada LucíaCubiella TamaraSan-Juan-Guardado JaimeSuárez-Priede ÁlvaroGómez-Suárez NereaSalerno LauraMurias EduardoDa Silva Torres MarinaWeiner Joshua AHerrada-Manchón HelenaFernández M AlejandroChiara María-Dolores - Neuroendocrine neoplasms (NENs) encompass tumors arising from neuroendocrine cells in various organs, including the gastrointestinal tract, pancreas, adrenal gland, and paraganglia. Despite advancements, accurately predicting the aggressiveness of gastroenteropancreatic (GEP) NENs based solely on pathological data remains challenging, thereby limiting optimal clinical management. Our previous research unveiled a crucial link between hypermethylation of the protocadherin PCDHGC3 gene and neuroendocrine tumors originating from the paraganglia and adrenal medulla. This epigenetic alteration was associated with increased metastatic potential and succinate dehydrogenase complex (SDH) dysfunction. Expanding upon this discovery, the current study explored PCDHGC3 gene methylation within the context of GEP-NENs in a cohort comprising 34 cases. We uncovered promoter hypermethylation of PCDHGC3 in 29% of GEP-NENs, with a significantly higher prevalence in gastrointestinal (GI) neuroendocrine carcinomas (NECs) compared with both pancreatic (Pan) NECs and neuroendocrine tumors (NETs) of GI and Pan origin. Importantly, these findings were validated in one of the largest multi-center GEP-NEN cohorts. Mechanistic analysis revealed that PCDHGC3 hypermethylation was not associated with SDH mutations or protein loss, indicating an SDH-independent epigenetic mechanism. Clinically, PCDHGC3 hypermethylation emerged as a significant prognostic factor, correlating with reduced overall survival rates in both patient cohorts. Significantly, whereas PCDHGC3 hypermethylation exhibited a strong correlation with TP53 somatic mutations, a hallmark of NEC, its predictive value surpassed that of TP53 mutations, with an area under the curve (AUC) of 0.95 (95% CI 0.83-1.0) for discriminating GI-NECs from GI-NETs, highlighting its superior predictive performance. In conclusion, our findings position PCDHGC3 methylation status as a promising molecular biomarker for effectively stratifying patients with GI-NENs. This discovery has the potential to advance patient care by enabling more precise risk assessments and tailored treatment strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. - Source: PubMed
Publication date: 2024/05/25
Cubiella TamaraCelada LucíaSan-Juan-Guardado JaimeRodríguez-Aguilar RaúlSuárez-Priede ÁlvaroPoch MaríaDominguez FranciscoFernández-Vega IvánMontero-Pavón PedroFraga Mario FNakatani YoichiroTakata SoYachida ShinichiValdés NuriaChiara María-Dolores - The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary between the cornea and sclera. Previously, we identified a mutation in a sclerocornea pedigree. Here, we investigated the impacts of on NCC activities during eye development. deficiency caused upregulation of . Both knockdown and upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that had 190.9-fold higher expression in scleral stroma than in corneal stroma. was also significantly upregulated by both knockdown and overexpression, and knock down of rescued the differentiation and migration of NCCs with deficiency. Consistently, overexpressing in led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression. - Source: PubMed
Publication date: 2024/05/03
Liu HongyanQi BenxiangLiu GuanghuiDuan HaoyunLi ZongyiShi ZhaoyingChen YonglongChu Wai KitZhou QingjunZhang Bi Ning - A genomic study was conducted to identify the effects of urbanization and environmental contaminants with heavy metals on selection footprints in dairy cattle populations reared in the megacity of Bengaluru, South India. Dairy cattle reared along the rural-urban interface of Bengaluru with/without access to roughage from public lakeshores were selected. The genotyped animals were subjected to the cross-population-extended haplotype homozygosity (XP-EHH) methodology to infer selection sweeps caused by urbanization (rural, mixed, and urban) and environmental contamination with cadmium and lead. We postulated that social-ecological challenges contribute to mechanisms of natural selection. A number of selection sweeps were identified when comparing the genomes of cattle located in rural, mixed, or urban regions. The largest effects were identified on BTA21, displaying pronounced peaks for selection sweeps for all three urbanization levels (urban_vs_rural, urban_vs_mixed and rural_vs_mixed). Selection sweeps are located in chromosomal segments in close proximity to the genes lrand rab interactor 3 (), solute carrier family 24 member 4 (), tetraspanin 3 (), and proline-serine-threonine phosphatase interacting protein 1 (). Functional enrichment analyses of the selection sweeps for all three comparisons revealed a number of gene ontology (GO) and KEGG terms, which were associated with reproduction, metabolism, and cell signaling-related functional mechanisms. Likewise, a number of the chromosomal segments under selection were observed when creating cattle groups according to cadmium and lead contaminations. Stronger and more intense positive selection sweeps were observed for the cadmium contaminated group, i.e., signals of selection on BTA 16 and BTA19 in close proximity to genes regulating the somatotropic axis (growth factor receptor bound protein 2 () and cell ion exchange (chloride voltage-gated channel 6 ()). A few novel, so far uncharacterized genes, mostly with effects on immune physiology, were identified. The lead contaminated group revealed sweeps which were annotated with genes involved in carcass traits (, , and ), milk yield (, , , and ), reproduction (), hypoxia/stress response ( and ), cell adhesion (), inflammatory response (), and immune defense mechanism (). Thus, the findings from this study provide a deeper insight into the genomic regions under selection under the effects of urbanization and environmental contamination. - Source: PubMed
Publication date: 2023/11/15
Velayudhan Silpa MullakkalparambilAlam ShahinYin TongBrügemann KerstinBuerkert AndreasSejian VeerasamyBhatta RaghavendraSchlecht EvaKönig Sven