Video Experimental Relacionado
Updated: Sep 20, 2025
11:27
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
16.8K
El factor de linaje renal PAX8 controla la señalización oncogénica en el cáncer de riñón
Saroor A Patel1,2, Shoko Hirosue1, Paulo Rodrigues1
1MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
Nature
|June 8, 2022
Resumen
El factor de transcripción del linaje PAX8 es esencial para el desarrollo del carcinoma renal de células claras (CCRCC). Media la señalización oncogénica tanto para mutaciones hereditarias como somáticas, lo que explica el riesgo de cáncer específico del tejido.
Área de la Ciencia:
- En el campo de la oncología
- La genética
- Biología molecular
Sus antecedentes:
- Las mutaciones cancerosas exhiben una fuerte selectividad tisular, pero los mecanismos subyacentes no se comprenden completamente.
- El carcinoma renal de células claras (CCRCC) es un cáncer renal común con factores genéticos conocidos.
- El papel de los factores de transcripción del linaje en el desarrollo de cáncer específico del tejido es un área activa de investigación.
Objetivo del estudio:
- Investigar el papel del factor de transcripción del linaje emparejado en la casilla 8 (PAX8) en la señalización oncogénica del ccRCC.
- Para aclarar cómo PAX8 media el riesgo de cáncer específico del tejido asociado con las variantes genéticas en ccRCC.
- Comprender la interacción entre PAX8, pérdida de VHL y HIF2A en la patogénesis de ccRCC.
Principales métodos:
- Modelos experimentales
- Genómica funcional
- Análisis de muestras de pacientes
- Pruebas de inmunoprecipitación por cromatina
- Análisis de la expresión génica
Principales resultados:
- PAX8 se requiere para la señalización oncogénica en ccRCC, impulsada por las dos variantes de la línea germinal (rs7948643) y la inactivación somática de la VHL.
- El factor 2α inducible por hipoxia (HIF2A) se recluta preferentemente con los potenciadores ligados a PAX8, incluido el potenciador CCND1.
- El alelo C protector de ccRCC en rs7948643 inhibe la unión a PAX8 y la expresión de CCND1.
- Los programas dependientes de PAX8 son cooptados para la expresión de MYC en metástasis de ccRCC.
Conclusiones:
- Los factores de transcripción de linaje como PAX8 son mediadores esenciales de la señalización oncogénica en el CCRCC.
- PAX8 juega un papel crítico en conferir el riesgo de cáncer específico del tejido tanto para las variantes genéticas somáticas como para las hereditarias.
- Comprender el papel de PAX8 proporciona información sobre el desarrollo de ccRCC y las posibles estrategias terapéuticas.
Más Videos Relacionados
07:38Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
286
07:44Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice
Published on: February 17, 2023
1.7K
Videos de Conceptos Relacionados
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
01:20The Retinoblastoma Gene
4.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
01:19Interactions Between Signaling Pathways
6.6K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K
02:23Abnormal Proliferation
4.6K
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...
4.6K
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
01:33Cancer-Critical Genes I: Proto-oncogenes
9.2K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K