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Ras impulsa la malignidad a través del cruce de células madre con el microambiente

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Las células madre del cáncer impulsan la progresión del carcinoma de células escamosas mediante la recableación de la expresión génica y la interacción de señales aberrantes con su microambiente, alimentando la malignidad. Esta interacción dinámica involucra vías cruciales para el crecimiento del tumor y la metástasis.

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Área de la Ciencia:

  • En el campo de la oncología
  • Biología del cáncer
  • Señales moleculares

Sus antecedentes:

  • Los carcinomas de células escamosas se desarrollan a partir de papilomas benignos, impulsados por la señalización RAS-MAPK.
  • Las células madre cancerosas (CSC) en las interfaces tumorales adquieren resistencia a las terapias.
  • El papel de los CSC en la progresión del carcinoma de células escamosas benigno al invasivo no se comprende completamente.

Objetivo del estudio:

  • Investigar el papel y los mecanismos de las células madre del cáncer en la conducción de la progresión del carcinoma de células escamosas.
  • Para aclarar la transmisión dinámica de señales entre los CSC y su microambiente durante la transformación maligna.

Principales métodos:

  • Utilizó un modelo de ratón HRASG12V de piel clonal.
  • Empleó transcriptómica de una sola célula, paisajismo de cromatina, reporteros lentivirales y rastreo de linaje.
  • Se han examinado funcionalmente las principales vías de señalización implicadas en las interacciones entre el CSC y el microambiente.

Principales resultados:

  • La activación oncogénica de RAS en las CSC desencadena la recableación de la expresión génica y la señal de cruce aberrante.
  • Esta interconexión activa la angiogénesis, el TGFβ, el receptor de leptina/leptina y las vías de señalización PI3K-AKT-mTOR.
  • Las interacciones temporales dinámicas entre los CSC y el microambiente son críticas para la progresión maligna.

Conclusiones:

  • Los intercambios intercelulares aberrantes y no genéticos orquestados por las CSCs alimentan la transición al carcinoma de células escamosas invasivo.
  • La comprensión de este cruce dinámico ofrece objetivos terapéuticos potenciales para cánceres avanzados.
  • Los conocimientos sobre las interacciones entre el CSC y el microambiente tienen amplias implicaciones para la terapia del cáncer.