Ask about this productRelated genes to: TM4SF4 antibody
- Gene:
- TM4SF4 NIH gene
- Name:
- transmembrane 4 L six family member 4
- Previous symbol:
- -
- Synonyms:
- il-TMP
- Chromosome:
- 3q25.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-16
- Date modifiied:
- 2016-10-05
Related products to: TM4SF4 antibody
Related articles to: TM4SF4 antibody
- Transmembrane 4 superfamily member 4 (TM4SF4) has been identified as a key regulator of epithelial-mesenchymal transition (EMT)-associated stemness in non-small cell lung cancer (NSCLC) cells through autocrine signaling involving insulin-like growth factor 1 (IGF1) and osteopontin (OPN). Given its pivotal role in tumor progression and therapy resistance, TM4SF4 represents a promising therapeutic target. To develop a therapeutic antibody against TM4SF4, we generated anti-TM4SF4 monoclonal antibodies in mice by targeting the large extracellular loop (LEL) of human TM4SF4 using a 15-mer peptide, hTM4SF4 (T126-E140). Among the generated clones, the 2B7 antibody exhibited high specificity and reactivity to TM4SF4. Mechanistic studies were conducted to evaluate the effects of 2B7 on key signaling pathways, EMT-associated stemness, immune checkpoint ligand (ICL) expression, and immune responses. To facilitate clinical translation, 2B7 was humanized, generating the Hz2B7-1.1 antibody, which underwent affinity maturation to select the lead candidate, Hz2B7-1.2. Functional assays, including antibody-dependent cellular cytotoxicity (ADCC) and preclinical evaluations in xenograft models, were performed to assess its therapeutic potential. The 2B7 antibody demonstrated significant antitumor efficacy in both A549 xenograft and patient-derived xenograft (PDX) models. Mechanistically, 2B7 inhibited key signaling pathways, including PI3K/AKT/GSK3β/β-catenin and JAK2/STAT3, leading to a reduction in EMT-associated stemness and therapy resistance. Additionally, 2B7 downregulated the expression of ICLs, such as PD-L1 and B7-H4, promoting T-cell activation and mitigating immune evasion. Furthermore, 2B7 reduced the secretion of exosomal ICLs by tumor cells and enhanced antitumor immune responses. The humanized antibody Hz2B7-1.2 retained binding properties and antitumor activity comparable to the parental 2B7 antibody and effectively induced ADCC as an IgG1-type antibody. The humanized anti-TM4SF4 antibody, Hz2B7-1.2, exhibits strong antitumor activity through multiple mechanisms, including inhibition of oncogenic signaling pathways, reduction of EMT-associated stemness, and modulation of immune responses. These findings support Hz2B7-1.2 as a promising therapeutic candidate for TM4SF4-positive cancers, warranting further clinical investigation. - Source: PubMed
Publication date: 2026/01/01
Kim Rae-KwonHeo Chang-KyuChoi Mun JuKahm Yeon-JeeKim Min KyuLee MinyongLee Ji YoonPark HwangseoJung UheeShin Byung-ChulKim Bum-JinKim Sung-ChulCho Eun-WieRyu Chun JeihKim In-Gyu - This study screened and identified gallstone disease (GSD) high-frequency mutation sites through sequencing of whole blood samples from 197 cases and 191 controls. Subsequently, a self-developed two-dimensional PCR (2D-PCR) method was employed to genotype the GSD susceptibility loci, which were determined through genome-wide association studies (GWAS), in 595 cases and 393 controls: TM4SF4 (rs9843304), GCKR (rs1260326), and CYP7A1 (rs6471717). We compared the genotype and allele frequencies among these groups, and performed univariate and multivariate logistic regression analyses to identify risk factors for GSD. The R programming language was used to develop a predictive model, validated through receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). After adjusting for sex and age, the rs9843304 TT genotype (OR: 0.51, 95 % CI: 0.36-0.74, P < 0.001) and and rs1260326 TT genotype (OR: 0.65, 95 % CI: 0.45-0.95, P = 0.03) were significantly associated with a lower risk of GSD compared to the CC genotype. Two nomograms were constructed and validated: (1) a comprehensive diagnostic model including liver-function tests, and (2) a streamlined predictive model excluding them. Discrimination, calibration and clinical utility were assessed with ROC curves, calibration plots and DCA. The full model achieved AUCs of 0.800 (training) and 0.806 (validation); the simplified model reached 0.713 and 0.746. Calibration curves indicated a good fit and DCA showed net-benefit thresholds of 0.38-1.00 (training) and 0.30-1.00 (validation) for the simplified model, and 0.18-1.00 for the full model. In summary, 2D-PCR offers an efficient, low-cost platform for GSD genetic screening, and the nomograms enable individualized risk prediction suitable for primary-care and health-check settings. - Source: PubMed
Publication date: 2025/09/10
Pan LiliYao ShuangZhu XuetingLuo Guanghua - The clinical application of cellular immunotherapy in hepatocellular carcinoma (HCC) is impeded by the lack of a cell surface target frequently expressed in HCC cells and with minimal presence in normal tissues to reduce on-target, off-tumor toxicity. To address this, an in silico multomics analysis was conducted to identify an optimal therapeutic target in HCC. A longlist of genes (n = 12,948) expressed in HCCs according to The Human Protein Atlas database were examined. Eight genes were shortlisted to identify one with the highest expression in HCCs, without being shed into circulation, and with restrictive expression profile in other normal human tissues. A total of eight genes were shortlisted and subsequently ranked according to the combination of their transcript and protein expression levels in HCC cases (n = 791) derived from four independent datasets. TM4SF4 was the top-ranked target with the highest expression in HCCs. TM4SF4 showed more favorable expression profile with significantly lower expression in normal human tissues but more highly expressed in HCC compared with seven other common HCC therapeutic targets. Furthermore, scRNA-seq and immunohistochemistry datasets showed that TM4SF4 was absent in immune cell populations but highly expressed in the bile duct canaliculi of hepatocytes, regions inaccessible to immune cells. In scRNA-seq dataset of HCCs, TM4SF4 expression was positively associated with mitochondrial components and oxidative phosphorylation Gene Ontologies in HCC cells (n = 15,787 cells), suggesting its potential roles in mitochondrial-mediated oncogenic effects in HCC. Taken together, TM4SF4 is proposed as a promising cell surface target in HCC due to its high expression in HCC cells with restricted expression profile in non-cancerous tissues, and association with HCC oncogenic pathways. - Source: PubMed
Publication date: 2025/02/25
Wong Kah KengAb Hamid Suzina Sheikh - Lung adenocarcinoma (LUAD) is one of the deadliest cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy is an important approach for treating LUAD. However, the development of acquired resistance poses a serious clinical challenge. Our objective was to explore the differentially expressed genes (DEGs) associated with EGFR and detect biomarkers for diagnosing and treating osimertinib resistance in LUAD patients. LUAD datasets were downloaded from public databases. Differential expression analysis was performed to screen DEGs, and prognostic modules were constructed by Cox regression. Enrichment analysis, gene regulatory network analysis and immune microenvironment analysis were employed to explore the underlying mechanisms in LUAD. Finally, the expression of prognosis module genes (PMGs) was validated in 8 LUAD tissue specimens and 5 cell lines by qRT-PCR. In total, 13 differential module genes (BIRC3, CCT6A, CPLX2, GLCCI1, GSTA1, HLA-DQB2, ID1, KCTD12, MUC15, NOTUM, NT5E, TCIM, and TM4SF4) were screened for the construction of a prognostic module. Notably, CCT6A and KCTD12 demonstrated excellent accuracy in the diagnosis of LUAD. Immune dysregulation and BIRC3, HLA-DQB2, KCTD12, and NT5E expression were significantly associated with invasive immune cells in LUAD patients. The expression level of CCT6A was highest in PC9-OR and H1975-OR cells, while the expression level of KCTD12 was highest in paracancerous tissue and HBE cells. The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, KCTD12 and CCT6A might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients. - Source: PubMed
Publication date: 2024/12/11
Li HaiwenYang LiYang QuanLiang ZhuSu WenmeiYu Lili - The incidence of papillary thyroid cancer (PTC) has been steadily rising, though the underlying mechanism remains unclear. This study aims to elucidate the biological role of TM4SF4 in the PTC progression. Our differential expression analysis indicated that TM4SF4 was significantly upregulated in PTC, which was corroborated in both our local cohort and the data from Human Protein Atlas. Additionally, clinical characteristics analysis and receiver operating characteristic curves (ROC) demonstrated that TM4SF4 served as a significant diagnostic marker for PTC. Correlation and enrichment analysis of TM4SF4-related partners suggested that it was involved in cell junction and cohesion processes. Furthermore, immune infiltration analysis revealed a positive correlation between TM4SF4 expression and the immune activation in PTC. Importantly, experiments demonstrated that TM4SF4 downregulation suppressed the proliferation and metastasis of PTC cell lines while inducing apoptosis. We further discovered that the AKT activator SC79 was able to reverse the malignant behaviors suppression caused by TM4SF4 knockdown, suggesting that TM4SF4 may promote PTC progression via the AKT pathway. In conclusion, our study highlights the oncogenic role of TM4SF4 in PTC and identifies it as a novel biomarker for diagnosis and treatment. - Source: PubMed
Publication date: 2024/11/04
Lin LizhiWen JialiangXu TianshengSi Yuhao