DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Human discs large-associated protein 5 (DLGAP5) is upregulated in lung adenocarcinoma (LUAD), correlating with poor prognosis and immune infiltration. Targeting DLGAP5 with AT9283 inhibits LUAD growth by downregulating PLK1, suggesting DLGAP5 as a therapeutic target.
Area Of Science
- Oncology
- Molecular Biology
- Bioinformatics
Background
- Human discs large-associated protein 5 (DLGAP5) is implicated in cell cycle regulation and cancer progression.
- Understanding DLGAP5's role in lung adenocarcinoma (LUAD) is crucial for developing targeted therapies.
Purpose Of The Study
- To investigate the prognostic value, immune implications, biological functions, and therapeutic targeting strategies of DLGAP5 in LUAD.
- To explore DLGAP5's role in LUAD cell proliferation and its relationship with Polo-like kinase 1 (PLK1).
Main Methods
- Utilized multiple databases (TCGA, GEO, CPTAC, Human Protein Atlas) for expression and clinical significance analysis.
- Performed bioinformatics analysis, network pharmacology, and in vitro/in vivo experiments to assess DLGAP5 function and identify inhibitors.
- Screened for DLGAP5 inhibitors using virtual screening and evaluated their efficacy in LUAD models.
Main Results
- DLGAP5 was highly expressed in LUAD, associated with poor prognosis, increased immune infiltration, and higher drug resistance.
- DLGAP5 promotes LUAD cell proliferation by upregulating PLK1; PLK1 can rescue DLGAP5 knockdown effects.
- AT9283 identified as a DLGAP5 inhibitor, effectively suppressing LUAD growth in vitro and in vivo, and its effects were linked to DLGAP5 and PLK1 expression.
Conclusions
- DLGAP5 is upregulated in LUAD, linked to poor prognosis and immune evasion.
- DLGAP5 promotes LUAD proliferation via PLK1, highlighting a potential therapeutic pathway.
- DLGAP5 inhibition by AT9283 shows promise as a therapeutic strategy for LUAD.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...