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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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La reprogramación asociada a la senescencia promueve el desarrollo del cáncer

Maja Milanovic1, Dorothy N Y Fan1,2,3,4, Dimitri Belenki1

  • 1Charité - Universitätsmedizin Berlin, Medical Department of Hematology, Oncology and Tumor Immunology, and Molekulares Krebsforschungszentrum - MKFZ, Virchow Campus, 13353 Berlin, Germany.

Nature
|December 21, 2017
PubMed
Resumen
Este resumen es generado por máquina.

La senescencia celular inducida por la quimioterapia puede aumentar inesperadamente la resistencia del cáncer, lo que lleva a tumores más agresivos y recaídas. Escapar a la senescencia aumenta el crecimiento de las células cancerosas y el potencial de iniciación de tumores.

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Área de la Ciencia:

  • En el campo de la oncología
  • Biología celular
  • Biología de las células madre del cáncer

Sus antecedentes:

  • La senescencia celular es una detención protectora del ciclo celular. Los reguladores clave de la senescencia también controlan las funciones de las células madre.
  • El aumento de la densidad en las células cancerosas puede impulsar la agresividad del tumor y los malos resultados clínicos.

Objetivo del estudio:

  • Investigar si la senescencia inducida por quimioterapia altera las propiedades relacionadas con las células madre en las células malignas.
  • Comprender las implicaciones de la senescencia asociada a la agresividad del cáncer y los resultados terapéuticos.

Principales métodos:

  • Expresión génica y análisis funcionales en linfomas de células B senescentes y no senescentes de ratones transgénicos Eμ-Myc.
  • Utilizó modelos genéticamente intercambiables dirigidos a H3K9me3 o p53 para estudiar el escape de la senescencia.
  • Se investigó la aplicación de la senescencia en modelos regulables por p53 de leucemia linfoblástica aguda y mieloide.

Principales resultados:

  • Los linfomas senescentes mostraron firmas de células madre adultas reguladas, señalización Wnt activada y marcadores de células madre distintos.
  • Las células que escaparon de la senescencia mostraron un crecimiento clonogénico mejorado y dependiente de Wnt y un mayor potencial de iniciación tumoral in vivo.
  • La inducción de la senescencia temporal reprogramó las células leucémicas no madre en células madre auto-renovadoras que inician la leucemia.

Conclusiones:

  • La senescencia asociada al tallo es una característica intrínseca que mejora la agresividad de las células cancerosas al liberarse de la detención del ciclo celular.
  • Este fenómeno tiene implicaciones significativas para la terapia del cáncer, particularmente en entornos de recaída.
  • Los hallazgos revelan la plasticidad de las células cancerosas y ofrecen nuevos conocimientos mecánicos sobre la recurrencia del tumor.