The PI3K/AKT axis modulates AATF activity in Wilms' tumor cells

Peng Jing1,2, Jiaqiong Zou3, Kegui Weng4

  • 1Department of Pediatric Surgery Affiliated Hospital of Northern Sichuan Medical College Nanchong China.

FEBS Open Bio
|October 20, 2018
PubMed

Insights

Apoptosis-antagonizing transcription factor (AATF) is highly expressed in Wilms' tumor (WT), promoting cancer growth and metastasis. Targeting AATF may offer a new therapeutic strategy for WT patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Apoptosis-antagonizing transcription factor (AATF) is overexpressed in various cancers, influencing tumor development and patient outcomes.
  • The role of AATF in Wilms' tumor (WT), a common pediatric kidney cancer, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression and functional significance of AATF in Wilms' tumor.
  • To explore the potential of AATF as a prognostic biomarker and therapeutic target in WT.

Main Methods:

  • Quantitative analysis of AATF expression in WT tissues versus normal tissues.
  • In vitro studies involving AATF knockdown and overexpression in WT cells to assess proliferation, invasion, and migration.
  • In vivo xenograft models to evaluate the effect of AATF knockout on tumor formation.
  • Investigation of the involvement of the phosphoinositide-3-kinase (PI3K)/AKT pathway in AATF-mediated effects.

Main Results:

  • AATF expression was significantly elevated in WT tissues compared to normal tissues.
  • High AATF levels correlated with increased risk of tumor relapse and pulmonary metastasis in WT patients.
  • AATF knockdown inhibited WT cell proliferation, invasion, and migration in vitro.
  • AATF overexpression promoted these aggressive cellular behaviors.
  • AATF knockout significantly reduced tumor growth in vivo.
  • The PI3K/AKT pathway was identified as a key regulator of AATF activity in WT.

Conclusions:

  • AATF is upregulated in Wilms' tumor and serves as a potential predictor of poor clinical outcomes.
  • AATF promotes WT development and progression through the PI3K/AKT signaling pathway.
  • AATF represents a promising diagnostic marker and therapeutic target for Wilms' tumor.

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