Ask about this productRelated genes to: TMEM158 Blocking Peptide
- Gene:
- TMEM158 NIH gene
- Name:
- transmembrane protein 158 (gene/pseudogene)
- Previous symbol:
- -
- Synonyms:
- RIS1, p40BBp
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2006-07-11
- Date modifiied:
- 2016-10-24
Related products to: TMEM158 Blocking Peptide
Related articles to: TMEM158 Blocking Peptide
- Cancer-associated fibroblasts (CAFs) are central to the pancreatic ductal adenocarcinoma (PDAC) microenvironment, promoting tumor progression and therapeutic resistance. However, the expression landscape of CAF membrane proteins in PDAC remains poorly defined. We integrated scRNA-seq (n = 33; 87,949 cells), spatial transcriptomics (n = 2; 7,011 spots), and bulk RNA-seq (n = 7; 642 samples) to systematically identify PDAC-specific CAF membrane genes. A LASSO-based Cox model was developed to construct a prognostic signature, PaFMS, and evaluated through multi-cohort validation. Functional enrichment, immune infiltration, drug sensitivity, and immunotherapy response analyses were further conducted. Validation was performed using multiple database-driven analyses. We identified a PDAC-enriched myoCAF-c1 cluster closely associated with epithelial-mesenchymal transition (EMT) and angiogenesis. From this cluster, 33 candidate CAF membrane genes were defined, whose protein-protein interactions were predominantly linked to extracellular matrix organization and collagen remodeling, and spatially colocalized with myoCAF-c1 and EMT regions. An 11-gene prognostic signature, PaFMS that robustly stratified patients across six independent cohorts, achieving high predictive accuracy for overall survival. High-risk patients exhibited proliferative signaling activation, immune suppression, and reduced T/B-cell infiltration. PaFMS was associated with responses to 33 anticancer agents and predicted enhanced benefit from anti-PD-L1 immunotherapy in the low-risk group. Multi-cohort validation confirmed the expression specificity of PaFMS genes, including PLAU, TMEM158, and TRIM59. Together, these findings reveal that myoCAF-c1 promotes angiogenesis and tumor progression, and establish PaFMS as a robust CAF membrane-based prognostic model in PDAC with potential utility for precision prognosis and therapeutic decision-making. KEY MESSAGES: Integrated single-cell, spatial, and bulk RNA-seq analyses identified PDAC-specific CAF membrane genes. Discovered a PDAC-enriched myoCAF-c1 subtype linked to EMT and angiogenesis. Developed an 11-gene CAF membrane-based prognostic model (PaFMS) validated across six cohorts. PaFMS predicts patient survival, drug sensitivity, and immunotherapy response in PDAC. - Source: PubMed
Publication date: 2026/04/06
Zhuang LeshiZhang WeiWu JunCao JianFeng LiangCao Shubo - Previous studies have demonstrated that the USP14 inhibitor IU1 and USP14/UCHL5 inhibitor b-AP15 can extend the survival period of TP53-deficient mice with spontaneous osteosarcoma (OS). However, the underlying molecular mechanisms remain to be fully elucidated. The transmembrane protein TMEM158 has been identified as a key regulator in the progression of various cancers. Nevertheless, its functional role in OS remains largely unknown. In this study, we conducted comprehensive bioinformatics analyses-including cluster analysis, differential expression analysis, and functional enrichment analysis-on clinical OS databases to assess the correlation between TMEM158 expression and the proteasome-associated USP14 and UCHL5. Primary tumor cells (TP53-deficient OS cells), SAOS-2 and U-2OS cells were treated with IU1 or b-AP15, respectively. The expression levels of TMEM158 were quantified using qPCR. Subsequently, TMEM158 was knocked down in three cell lines, and subsequent changes in cellular activity and TGF-β signaling were evaluated. Concurrently, single-cell RNA sequencing data were analyzed to identify cell types exhibiting high TMEM158 expression and to explore their associated intercellular communication patterns. Both IU1 and b-AP15 significantly prolonged the survival of TP53-deficient OS mice and exhibited enhanced cytotoxic effects on TP53-deficient OS cells. These compounds selectively suppressed TMEM158 expression in TP53-deficient primary OS and SAOS-2 cells. Bioinformatics analysis revealed that TMEM158 is positively correlated with USP14 and UCHL5 expression and serves as an independent prognostic marker for poor clinical outcomes in OS patients. Experimental validation showed that TMEM158 knockdown significantly reduced the viability of TP53-deficient primary OS and SAOS-2 cells, and inhibited TGF-β pathway activation. Osteoblastic OS cells displayed concurrent suppression of the P53 pathway and activation of the TGF-β pathway, with a strong covariant relationship between TMEM158 and activity of TGF-β pathway. Meanwhile, there may be intercellular TGF-β signaling communication between osteoblastic OS cells with high expression levels of TMEM158 and macrophages. Our findings demonstrated that the TMEM158-TGF-β pathway plays a central role in mediating the heightened sensitivity of TP53-deficient OS to USP14 inhibition. Targeting this pathway may represent a promising therapeutic strategy for precision treatment of osteosarcoma. - Source: PubMed
Publication date: 2026/02/05
Chen Zi-YuYasen MiersalijiangJiang Song-YaoYe Zi-YiYang Qin-XinLu Cui-NiShi YiLiu Xin-YunDu Ting-TingTang Xiao-MeiFu DaMa Yu-ShuiYu HongWang Xiao-Feng - In cancer research, the transmembrane (TMEM) family of proteins has attracted considerable attention due to its role in tumor progression and chemoresistance. These membrane proteins are integral to cellular processes, including signal transduction, ion transport and cellular homeostasis, rendering them promising therapeutic targets. The TMEM proteins are implicated in several types of cancer, including breast, ovarian, lung and thyroid cancer, where they regulate numerous cellular processes, including proliferation, migration, invasion and survival. Notably, TMEM45A and TMEM158 contribute to resistance to platinum‑based chemotherapy by increasing the expression of proteins associated with hypoxic conditions and multidrug resistance. Additionally, epigenetic regulation, particularly promoter methylation of TMEM88, is pivotal in regulating TMEM88 expression and function in chemoresistance. The present review presents a systematic and comprehensive overview of the structural features, biological functions and regulatory mechanisms of key TMEM proteins across various types of cancer. It also highlights emerging connections between TMEM proteins and the tumor microenvironment, emphasizing their potential as promising therapeutic targets. The novel findings underscore the key role of the TMEM protein family in overcoming chemoresistance and lay a foundation for the development of targeted therapeutic strategies in cancer treatment. - Source: PubMed
Publication date: 2025/10/10
Shi JiZheng DuoYao BingLiu QiangXu HuizhePiao Haozhe - Arsenic is a contaminant in drinking water and food, and exposure induces inflammation and barrier disruption in the small intestine and colon. Further, arsenic can alter stromal cell numbers and their signaling molecules in the duodenum. Thus, the goal of this study was to investigate arsenic's effects on morphology, Pdgfrα stromal cell numbers, localization, and signaling in the ileum. Mice were exposed to 0, 100, and 500 ppb arsenic for 13 weeks, and intestinal sections, including the ileum, dissected out. The results show that arsenic dose-responsive increases in crypt budding and macrophage numbers in the ileum. Arsenic exposure also increased transcript expression of telocyte (Cd201, Tmem158, Wnt4), trophocyte (Ackr4, Grem1), Igfbp5+ fibroblast (Igfbp5), and Fgfr2+ fibroblast (Fgfr2, Igfbp3, Wnt4) markers in the ileum of female mice, but not in the males. Linear regression indicated that markers of telocytes and Fgfr2+ fibroblasts significantly correlated with Wnt4 expression. IHC revealed the numbers of telocytes within the villi of male and females were increased by 6.3- and 2.3-fold at 500 ppb, respectively. Linear regression of Grem1 versus Bmp4 protein expression revealed significant correlation, with arsenic exposed females having higher expression of both signaling molecules. Overall, the results suggest that Pdgfrα+ stromal cells in the ileum play vital roles in maintaining intestinal stem cell (ISC) and epithelial homeostasis in response to arsenic, and that sex-dependent changes in responses exist. - Source: PubMed
Publication date: 2025/09/29
Ventrello Scott WLea Kayla ABain Lisa J - This study aims to elucidate the molecular mechanisms underlying acrylamide-induced colorectal cancer (CRC), identify key carcinogenic genes, and investigate their roles in the immune microenvironment and gut microbiota, providing a theoretical foundation for early CRC diagnosis and prevention. - Source: PubMed
Publication date: 2025/05/10
Yu XiaopengNiu JunjieHu Jinyang