Video Experimental Relacionado
Updated: Sep 10, 2025
07:46
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
25.4K
El complejo NRF2-SOX4 regula la PSPH en el carcinoma hepatocelular y modula la diferenciación de los macrófagos M2
Chi-Neu Tsai1,2, Ming-Chin Yu2,3, Yun-Shien Lee4
1Graduate Institute of Clinical Medical Science, Chang-Gung University, Taoyuan City, Taiwan.
Cancer gene therapy
|August 26, 2025
Resumen
Un nuevo eje SOX4-NRF2-PSPH regula el metabolismo del carcinoma hepatocelular (HCC) y la evasión inmune. Dirigirse a esta vía puede ofrecer nuevas terapias de HCC al interrumpir el apoyo de las células cancerosas y la supresión inmune.
Área de la Ciencia:
- En el campo de la oncología
- Biología molecular
- Metabolismo del cáncer
Sus antecedentes:
- La progresión del carcinoma hepatocelular (HCC) incluye reprogramación metabólica y evasión inmune.
- Las redes de transcripción que impulsan estos procesos de HCC no se comprenden completamente.
Objetivo del estudio:
- Identificar nuevas redes reguladoras que vinculan el metabolismo y la evasión inmune en el CHC.
- Para aclarar el papel de SOX4, NRF2 y fosfoserina fosfatasa (PSPH) en el HCC.
Principales métodos:
- Pruebas de coinmunoprecipitación y de ligadura de proximidad para confirmar los complejos proteicos.
- Pruebas de reporte de luciferasa y de inmunoprecipitación de cromatina para evaluar la regulación génica.
- Análisis de los datos de pacientes con CHC (TCGA y cohortes clínicas).
Principales resultados:
- SOX4 forma un complejo de respuesta al estrés con NRF2, activando la transcripción de PSPH.
- La PSPH mejora la biosíntesis de serina, apoyando la fosforilación oxidativa y el equilibrio redox.
- La inhibición de SOX4/NRF2 aumenta el daño oxidativo y la sensibilidad al sorafenib en las células de HCC.
- Los metabolitos impulsados por PSPH promueven la polarización de los macrófagos tipo M2, creando un microambiente tumoral inmunosupresor.
- Una alta expresión de SOX4/NRF2/PSPH se correlaciona con la infiltración M2 y un mal pronóstico de HCC.
Conclusiones:
- Un nuevo bucle regulador SOX4-NRF2-PSPH acopla el metabolismo del HCC con la modulación inmune.
- Este eje representa un objetivo terapéutico potencial para el tratamiento del CHC.
Videos de Conceptos Relacionados
02:26NF-κB-dependent Signaling Pathway
7.8K
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...
NF-κB-dependent Signaling Mechanism
The...
7.8K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
02:23Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
03:03mTOR Signaling and Cancer Progression
3.9K
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...
The mTOR pathway or the...
3.9K
01:24Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
01:31Transducer Mechanism: Nuclear Receptors
1.6K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.6K