laptm4b

BACKGROUND: Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, while supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome and congenital anomalies. Inositol status may be influenced by diet, synthesis, transport, utilisation and catabolism...

Esophageal carcinoma (ESCA) is one of the most prevalent and aggressive malignancies of the gastrointestinal tract and constitutes sixth primary cause of cancer-related death worldwide. It is urgently needed to identify effective therapeutic targets. Differentially expressed genes (DEGs) involved in ESCA were identified via bioinformatics analysis. Four DEGs were selected for further analysis using Gene Expression Profiling Interactive Analysis, Human Protein Atlas, UALCAN web portal, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis...

Mutations in DNAJC5/CSPα are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent s torage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS...

Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity...

Many computational pipelines exist for the detection of differentially expressed genes. However, computational pipelines for functional gene detection rarely exist. We developed a new computational pipeline for functional gene identification from transcriptome profiling data. Key features of the pipeline include batch effect correction, clustering optimization by gap statistics, gene ontology analysis of clustered genes, and literature analysis for functional gene discovery. By leveraging this pipeline on RNA-seq datasets from two mouse retinal development studies, we identified 7 candidate genes involved in the formation of the photoreceptor outer segment...

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed...

PURPOSE/OBJECTIVE(S): Approximate 25% of patients with local advanced head and neck cell carcinoma (HNSCC) treated with radiation still suffer from local relapse and are considered radiation resistant. We previously determined that radiation induces autophagy, a pro-survival cellular stress response, in HNSCC. In this study, we examine the consequence of autophagy inhibition and investigate the molecular mechanism underlying RT-induced autophagy. MATERIALS/METHODS: Autophagy was assessed using a nano-Luc LC3 reporter assay (Promega), immunoblotting and immunofluorescence for LC3 and acridine orange in multiple HNSCC cell lines...

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs)...

Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Due to the complicated etiology and lack of significant early symptoms, the diagnosis and treatment of bladder cancer is difficult. Lysosome-associated transmembrane protein 4β (LAPTM4B) was reported to be involved in the development and progression of several types of tumor, however, its potential effect on the development and metastasis of bladder cancer is still unclear. Immunohistochemistry was performed to detect the protein expression level of LAPTM4B in bladder cancer tissues and short hairpin RNAs targeting LAPTM4B were transfected into bladder cancer cells to knockdown its expression...

OBJECTIVE: LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B . This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on...

Broad-spectrum detection and long-term monitoring of circulating tumor cells (CTCs) remain challenging due to the extreme rarity, heterogeneity, and dynamic nature of CTCs. Herein, a dual-affinity nanostructured platform was developed for capturing different subpopulations of CTCs and monitoring CTCs during treatment. Stepwise assembly of fibrous scaffolds, a ligand-exchangeable spacer, and a lysosomal protein transmembrane 4 β (LAPTM4B)-targeting peptide creates biomimetic, stimuli-responsive, and multivalent-binding nanointerfaces, which enable harvest of CTCs directly from whole blood with high yield, purity, and viability...

OBJECTIVE: Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18 F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. METHODS: A PET targeting tracer named [18 F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18 F]fluoropropionate ([18 F]NFP)...

Acute Myeloid Leukemia (AML) is a heterogeneous neoplasm characterized by cytogenetic and molecular alterations that drive patient prognosis. Currently established risk stratification guidelines show a moderate predictive accuracy, and newer tools that integrate multiple molecular variables have proven to provide better results. In this report, we aimed to create a new machine learning model of AML survival using gene expression data. We used gene expression data from two publicly available cohorts in order to create and validate a random forest predictor of survival, which we named ST-123...

Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is a four-membrane spanning ceramide interacting protein that regulates mTORC1 signaling. Here, we show that LAPTM4B is sorted into intraluminal vesicles (ILVs) of multivesicular endosomes (MVEs) and released in small extracellular vesicles (sEVs) into conditioned cell culture medium and human urine. Efficient sorting of LAPTM4B into ILV membranes depends on its third transmembrane domain containing a sphingolipid interaction motif (SLim). Unbiased lipidomic analysis reveals a strong enrichment of glycosphingolipids in sEVs secreted from LAPTM4B knockout cells and from cells expressing a SLim-deficient LAPTM4B mutant...

Exosomes are extracellular vesicles that mediate the transport of intracellular molecules, including neurodegenerative agents. Exogenously administrated ceramides have been implicated in the acceleration of exosome production by neurons; however, the molecular machinery involved in this process is unknown. Here, we found that ceramides, especially those consisting of long fatty acids, were internalized into the endocytic pathway in neuroblastoma SH-SY5Y cells to induce exosome secretion through lysosome-associated protein transmembrane 4B (LAPTM4B)...

A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division...

Melanoma, which originates from the transformation of normal melanocytes, is one of the three main types of skin cancer. We aimed to explore the functions of SNHG16 and miR-132 in melanoma. CCK-8, Transwell assays were used to measure the viability and migration, respectively. Spearman's correlation analysis was performed to analyze the relationship between the expression of SNHG16, miR-132 and LAPTM4B in melanoma tissues. SNHG16 was overexpressed, and miR-132 was low expressed in melanoma tissues and cell lines...

Purpose: Long non-coding RNA P73 antisense RNA 1T (TP73-AS1) is a newly discovered lncRNA involved in the occurrence and development of several cancers. However, its role in lung cancer has not been well investigated yet. Methods: The expressions of TP73-AS1, microRNA-27b-3p (miR-27b-3p) and lysosomal-associated protein transmembrane-4 Beta (LAPTM4B) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V-FITC/PI and transwell assays, respectively...

RATIONALE: Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored. OBJECTIVE: To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury. METHODS AND RESULTS: LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury...

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. High Akt activation and aberrant β-catenin expression contribute to HCC cell proliferation, stem cell generation, and metastasis. Several signaling pathway-specific inhibitors are in clinical trials and display different efficacies against HCC. In this study, we observed that a β-catenin inhibitor (FH535) displays antiproliferative effect on transformed human hepatocytes (THH). A combination treatment of these cells with FH535 and Akt inhibitor (AZD5363) exerted a stronger effect on cell death...