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Melanoma is an unpredictable, highly metastatic malignancy, and treatment of advanced melanoma remains challenging. Novel molecular markers based on the alterations in gene expression and the molecular pathways activated or deactivated during melanoma progression are needed for predicting the course of the disease already in primary tumors and for providing new targets for therapy. Here, we sought to identify genes whose expression in primary melanomas correlate with patient disease-specific survival using global gene expression profiling. Many of the identified potential markers of poor prognosis were associated with the epithelial-mesenchymal transition, extracellular matrix formation, and angiogenesis. We studied further the significance of one of the genes, prolyl 4-hydroxylase subunit alpha 1 (P4HA1), in melanoma progression. P4HA1 depletion in melanoma cells reduced cell adhesion, invasion, and viability in vitro. In melanoma xenograft assays, we found that P4HA1 knockdown reduced melanoma tumor invasion as well as the deposition of collagens, particularly type IV collagen, in the interstitial extracellular matrix and in the basement membranes of tumor blood vessels, leading to vessel wall rupture and hemorrhages. Further, P4HA1 knockdown reduced the secretion of collagen triple helix repeat containing 1 (CTHRC1), an important mediator of melanoma cell migration and invasion, in vitro and its deposition around tumor blood vessels in vivo. Taken together, P4HA1 is an interesting potential prognostic marker and therapeutic target in primary melanomas, influencing many aspects of melanoma tumor progression.
This article was published in the following journal.
Name: Molecular oncology
Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a critical role in modulating the extracellular matrix and promoting tumor progression in various cancers. However, the association between P4HA1 and...
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Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accuratel...
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The purpose of this multi-center event-driven study in participants with anemia associated with chronic kidney disease (CKD) to evaluate the safety and efficacy of daprodustat.
The aim of this study is to assess the implicitement of the cholesterol 24 S hydroxylase gene and the 24 S hydroxycholesterol in glaucoma and in age related macular degeneration.
You are being asked to take part in this research registry because you or your family member is suspected to have a 24-hydroxylase deficiency.
Oral supplementation with enzymes that can cut gluten has been suggested as a potential treatment modality for coeliac disease. In the present study the investigators wish to determine if ...
Development of a new MS-based biomarker for the early and sensitive diagnosis of Mannosidosis alpha from plasma
Compounds that inhibit the action of HYDROXYLASES that act on PROLINE to form HYDROXYPROLINE.
A low affinity interleukin-5 receptor subunit that combines with the CYTOKINE RECEPTOR COMMON BETA SUBUNIT to form a high affinity receptor for INTERLEUKIN-5. Several isoforms of the interleukin-5 receptor alpha subunit exist due to multiple ALTERNATIVE SPLICING.
A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.
A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl-containing-peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.
An epithelial neoplasm characterized by unusually large anaplastic cells. It is highly malignant with fulminant clinical course, bizarre histologic appearance and poor prognosis. It is most common in the lung and thyroid. (From Stedman, 25th ed & Segen, Dictionary of Modern Medicine, 1992)
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...