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Related Concept Videos

Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

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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.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
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  1. Home
  3. Chemotherapy-induced S100a10 Recruits Kdm6a To Facilitate Oct4-mediated Breast Cancer Stemness.
  1. Home
  3. Chemotherapy-induced S100a10 Recruits Kdm6a To Facilitate Oct4-mediated Breast Cancer Stemness.

Related Experiment Video

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
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Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness.

Haiquan Lu1,2, Yangyiran Xie1, Linh Tran1

  • 1Vascular Program, Institute for Cell Engineering.

The Journal of Clinical Investigation
|May 20, 2020

View abstract on PubMed

Summary
This summary is machine-generated.

Chemotherapy can increase breast cancer stem cells (BCSCs) by activating pluripotency factors. This study reveals a hypoxia-inducible factor 1 (HIF-1) pathway that epigenetically regulates these factors, offering new therapeutic targets.

Keywords:
Breast cancerOncologyTranscriptionhypoxia

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Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Breast cancer stem cells (BCSCs) drive tumor recurrence and metastasis.
  • Chemotherapy can paradoxically enhance BCSC populations by upregulating pluripotency factors.
  • The precise regulatory mechanisms of this chemotherapy-induced BCSC enrichment remain unclear.

Purpose of the Study:

  • To elucidate the epigenetic pathway regulating pluripotency factor gene expression in BCSCs following chemotherapy.
  • To identify key molecular players involved in chemotherapy-induced BCSC specification.
  • To explore potential therapeutic strategies targeting this pathway for improved breast cancer treatment.

Main Methods:

  • Investigated the role of hypoxia-inducible factor 1 (HIF-1) in response to paclitaxel treatment.
  • Analyzed the formation of protein complexes involving S100A10, ANXA2, SPT6, and KDM6A.
  • Examined the epigenetic modification of H3K27me3 at pluripotency factor gene loci (OCT4, NANOG, SOX2, KLF4).
  • Utilized gene silencing and pharmacological inhibition of KDM6A to assess functional impact.

    • Main Results:

    • Paclitaxel treatment induced HIF-1-dependent S100A10 expression, forming a complex with ANXA2, SPT6, and KDM6A.
    • This complex was recruited to OCT4 binding sites, where KDM6A removed H3K27me3 marks, promoting NANOG, SOX2, and KLF4 transcription.
    • Silencing key pathway components or inhibiting KDM6A blocked chemotherapy-induced BCSC enrichment, impaired tumor initiation, and delayed recurrence.
    • Pharmacological inhibition of KDM6A also reduced BCSC populations post-chemotherapy.

    Conclusions:

    • A novel HIF-1/S100A10-ANXA2-SPT6-KDM6A pathway epigenetically activates pluripotency factors in response to chemotherapy.
    • This pathway is crucial for chemotherapy-induced BCSC enrichment and subsequent tumor progression.
    • Targeting this epigenetic mechanism, particularly KDM6A, in combination with chemotherapy may offer a strategy to overcome BCSC-mediated treatment resistance and improve patient outcomes.