Ask about this productRelated genes to: PHLDA1 antibody
- Gene:
- PHLDA1 NIH gene
- Name:
- pleckstrin homology like domain family A member 1
- Previous symbol:
- -
- Synonyms:
- TDAG51, DT1P1B11, PHRIP
- Chromosome:
- 12q15
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-19
- Date modifiied:
- 2016-01-27
Related products to: PHLDA1 antibody
Related articles to: PHLDA1 antibody
- The emphysematous phenotype is an important phenotype in chronic obstructive pulmonary disease (COPD), with substantial morbidity and mortality. The mechanisms underpinning the role of alveolar type II (AT2) cells in alveolar repair within this phenotype remain poorly understood. This study aimed to elucidate the role of PHLDA1, a potential stemness regulator in AT2 cells, on emphysema development. Utilizing mice model, we performed a targeted knockdown of PHLDA1 in AT2 cells and subsequently exposed these mice to tobacco smoke to assess the resultant severity of emphysema and related alveolar damage. We manipulated PHLDA1 expression in AT2 cells line or primary mouse AT2 cells to examine its influence on AT2 stemness-related processes- differentiation, proliferation, and wound closure ability. The specific pathway of PHLDA1 mediated in AT2 cells, as well as its interaction with the GLI1 protein, was further investigated. Mice with reduced PHLDA1 expression developed the emphysema independent of smoking exposure. PHLDA1 knockdown in AT2 cells attenuated their proliferation via the Hedgehog pathway, impairing wound closure ability in the emphysematous phenotype. We also discovered a binding relationship between PHLDA1 and GLI1, where PHLDA1 modulates the nuclear translocation of GLI1, thus regulating the Hedgehog pathway and influencing the stemness and proliferation of AT2 cells. Our study suggests that PHLDA1 is a critical factor in the proliferation process of AT2 cells via modulation of GLI1 nuclear translocation. This regulation is essential to the pathogenesis of the emphysematous phenotype in COPD, signifying potential therapeutic targets for intervention. - Source: PubMed
Publication date: 2026/07/04
Bai ShuangWang ShuaifuYe RuiWang DiMa MingxinZhao Li - Excessive lipid accumulation is a hallmark of metabolic disorders which includes obesity and insulin resistance; however, effective therapeutic strategies remain limited. Tamarixetin (Tx), a naturally occurring flavonoid with diverse pharmacological properties, has not been fully characterized in the context of lipid metabolism. In this study, we explored the metabolic benefits and molecular mechanisms of Tx in a Western diet (WD)-induced obesity model. Transcriptomic profiling revealed that Tx reversed WD-induced gene expression patterns, notably suppressing and inducing expression. Mechanistically, docking analysis suggested that Tx interacts with the acetyl-CoA-binding region within the p300 histone acetyltransferase domain, thereby attenuating H3K9 acetylation at the Pdk4 promoter. This epigenetic inhibition of led to activation of the p38/AMPK signaling cascade, upregulation of and , and enhanced insulin sensitivity . Collectively, our findings identify Tx as a novel epigenetic modulator that simultaneously suppresses lipogenic gene expression and restores metabolic signaling. Given its natural origin and multifaceted mode of action, Tx emerges as a promising candidate for therapeutic intervention in metabolic disorders. - Source: PubMed
Publication date: 2026/06/30
Song Ji-HyeLee JanghoKim Hyo-JinLee Jae-InLee Yu GeonChoi Hyo-KyoungHwang Jin-Taek - Cervical cancer is the fourth most common cancer among women worldwide and is often diagnosed at advanced stages, highlighting the need for effective systemic therapies, including those targeting key cancer-related pathways. Fibroblast growth factor (FGF) signalling plays a critical role in cell biology, activating FGF receptors (FGFRs) to regulate proliferation, migration and apoptosis. Aberrant activation of the pathway contributes to tumour progression in many cancers, including cervical cancer. FGFR inhibitors (FGFRi) have shown clinical promise but are limited by emergence of therapeutic resistance. Here, we describe mechanisms underpinning FGFRi resistance in three human cervical cancer cell lines (CaSki, HeLa, and SiHa). Transcriptomic analysis identified several genes differentially expressed between parental and resistant lines, including downregulation of Pleckstrin Homology Like Domain Family A Member 1 ( and upregulation of Phospholipase C beta 4 (, changes that associate with a metastatic phenotype. Protein interaction network analysis revealed integrin α2 (ITGA2) as a putative central node. Increased cytoplasmic localisation of ITGA2 and concomitant loss at cell-cell contacts, alongside focal adhesion kinase (FAK) activation was observed in PD173074 resistant cells. Moreover, resistant cell lines exhibited elevated S6 ribosomal protein (p-S6) phosphorylation, which persisted despite inhibition of FGFR, FAK or mammalian target of rapamycin complex 1 (mTORC1). Collectively, these findings suggest that FGFR inhibitor resistance in cervical cancer is associated with ITGA2-FAK signalling and AKT-independent mTOR activation, offering potential for overcoming therapeutic resistance via combinatorial treatment strategies. - Source: PubMed
Publication date: 2026/06/04
Bou Antoun NaufGrose Richard PWalker Anthony JModjtahedi HelmoutChioni Athina Myrto - - Source: PubMed
Publication date: 2026/06/03
Fearon Abbie ECarter Edward PClayton Natasha SWilkes Edmund HBaker Ann-MarieKapitonova EkaterinaBakhouche Bakhouche ATanner YasmineWang JunGadaleta EmanuelaChelala ClaudeMoore Kate MMarshall John FChupin JulietteSchmid PeterJones J LouiseLockley MichelleCutillas Pedro RGrose Richard P - Head and neck squamous cell carcinoma (HNSC) is a leading cause of morbidity and mortality worldwide. The roles of PHLDA genes in HNSC progression remain unclear. This study explores their expression, mutational landscape, and functional roles as potential diagnostic biomarkers and therapeutic targets. Eight HNSC cell lines and six normal oral keratinocyte cell lines were cultured, and RNA extraction and RT-qPCR analysis were conducted. The GSCA database validated gene expression in clinical HNSC samples. Methylation and survival analysis were performed using TCGA data, with survival correlation assessed via the KM Plotter tool and UALCAN database. Mutational analysis was done via cBioPortal, and immune-related correlations were analyzed using TISIDB. Functional assays were performed after siRNA-mediated knock down of PHLDA genes in SCC9 and SCC25 cells, including Western blot, CCK-8, colony formation, and wound healing assays. Our results demonstrate that PHLDA1, PHLDA2, and PHLDA3 are significantly upregulated in HNSC cell lines compared with normal controls, with PHLDA1 showing the most substantial increase. ROC analysis revealed that PHLDA1 exhibited the highest diagnostic potential for distinguishing HNSC from normal tissues. Methylation analysis showed hypomethylation of PHLDA genes in tumor tissues, particularly in the promoter regions. Higher expression of PHLDA genes correlated with poorer overall survival outcomes in HNSC patients. Mutational analysis revealed that PHLDA2 exhibited the highest mutation rate, with predominantly missense mutations. The PPI network analysis indicated that PHLDA genes interact with several cancer-related proteins, and DAVID analysis showed their involvement in processes like cell cycle regulation and tumorigenesis. Functional assays demonstrated that silencing of PHLDA genes in HNSC cells significantly impaired cell proliferation, clonogenic potential, and migration, suggesting their role as oncogenic regulators. Our study identifies PHLDA1, PHLDA2, and PHLDA3 as potential diagnostic biomarkers and therapeutic targets in HNSC. These genes are involved in critical pathways related to cancer progression and immune modulation. The findings suggest that targeting PHLDA genes may provide a novel approach for overcoming therapeutic resistance and improving patient outcomes in HNSC. - Source: PubMed
Publication date: 2026/05/26
Abdel-Maksoud Mostafa AAlamri AbdulazizFahad AljawharahAlrokayan SalmanAufy MohammedKiani Bushra HafeezZhang HanyongAyaz Muhammad MazharHameed YasirAlmutairi Saeedah