Loss of LRP1 Promotes Hepatocellular Carcinoma Progression via UFL1-Mediated Activation of NF-κB Signaling
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.Low-density lipoprotein receptor-related protein-1 (LRP1) suppresses hepatocellular carcinoma (HCC) progression. Reduced LRP1 levels increase tumor growth by promoting OGA degradation and NF-κB signaling, suggesting LRP1 as a therapeutic target for HCC.
Area Of Science
- Molecular Oncology
- Hepatocellular Carcinoma Pathogenesis
Background
- Low-density lipoprotein receptor-related protein-1 (LRP1) is implicated in hepatocellular carcinoma (HCC) invasion and metastasis.
- The precise molecular mechanisms linking LRP1 to HCC progression are not fully understood.
Purpose Of The Study
- To elucidate the role of LRP1 in HCC progression and identify its underlying molecular mechanisms.
- To investigate the therapeutic potential of targeting LRP1 in HCC treatment.
Main Methods
- Assessed LRP1 expression in HCC tissues and correlated it with clinical outcomes.
- Utilized LRP1 knockdown and overexpression models in HCC cell lines and in vivo studies.
- Investigated the interaction between LRP1, UFL1, OGA, and NF-κB signaling pathways using biochemical assays.
Main Results
- Lower LRP1 levels were significantly associated with advanced HCC malignancy and poor patient prognosis.
- LRP1 knockdown enhanced HCC cell tumorigenicity, while LRP1 or its β-chain overexpression inhibited it.
- LRP1 knockdown led to OGA degradation via UFL1, increasing O-GlcNAcylation of NF-κB and suppressing apoptosis.
- The LRP1 β-chain stabilized OGA, counteracting the anti-apoptotic effects mediated by NF-κB signaling.
Conclusions
- LRP1, particularly its β-chain, acts as a crucial regulator of OGA protein stability.
- LRP1 suppresses HCC progression by inhibiting NF-κB signaling through OGA stabilization.
- LRP1 represents a novel therapeutic target for attenuating HCC progression.
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 transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
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...
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
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...