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New STAT3-FOXL2 pathway and its function in cancer cells

Yangyang Han1, Jun Wu2, Weiwei Yang3

  • 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China. hanyy2009@163.com.

BMC Molecular and Cell Biology
|June 22, 2019
PubMed
Abstract

Insights

Signal transducer and activator of transcription 3 (STAT3) regulates the forkhead transcription factor (FOXL2) in cancer cells. This STAT3-FOXL2 pathway is crucial for regulating cancer cell apoptosis, offering new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The forkhead transcription factor (FOXL2) is vital for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), sex determination, ovarian development, and cell cycle control.
  • While FOXL2's downstream targets are studied, its upstream regulation remains largely unknown.

Purpose of the Study:

  • To investigate the upstream regulation of FOXL2.
  • To explore the role of STAT3 in regulating FOXL2.
  • To determine the functional significance of the STAT3-FOXL2 interaction in cancer cell apoptosis.

Main Methods:

  • Electrophoretic mobility shift assay (EMSA) to confirm STAT3 binding to FOXL2.
  • Chromatin immunoprecipitation (ChIP) to identify the binding site of STAT3 on FOXL2.
  • Gene knockdown experiments to assess the impact of STAT3 and FOXL2 on cancer cell apoptosis.

Main Results:

  • STAT3 was identified as a regulator of FOXL2 in cancer cells.
  • STAT3 directly binds to the FOXL2 gene promoter at a specific DNA sequence.
  • Knockdown of either STAT3 or FOXL2 significantly increased cancer cell apoptosis.
  • Apoptosis induction was associated with altered expression of apoptosis-related genes like TNF, TRAIL, and GnRHR.

Conclusions:

  • This study identifies STAT3 as a novel upstream regulator of FOXL2.
  • The STAT3-FOXL2 pathway plays a significant role in regulating apoptosis in HeLa cells.
  • These findings provide new insights for targeting FOXL2 in cancer prevention and treatment strategies.
Keywords:
Cell apoptosisSTAT3-FOXL2 pathwaySignal transductionTranscriptional regulation

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