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Contribution of KCTD12 to esophageal squamous cell carcinoma

Mohammad Reza Abbaszadegan1,2, Negin Taghehchian1,2, Liping Li3

  • 1Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

BMC Cancer
|August 31, 2018
PubMed
Abstract

Insights

Potassium channel tetramerization domain containing 12 (KCTD12) suppresses key cancer pathways in esophageal squamous cell carcinoma (ESCC). This finding suggests KCTD12 as a potential therapeutic marker for ESCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Potassium channel tetramerization domain containing 12 (KCTD12) is a known regulator of GABAB receptor signaling.
  • KCTD12 expression is inversely correlated with gastrointestinal stromal tumors.
  • The role of KCTD12 in esophageal squamous cell carcinoma (ESCC) signaling pathways and chromatin remodelers requires investigation.

Purpose of the Study:

  • To investigate the role of KCTD12 in regulating signaling pathways and chromatin remodelers in ESCC.
  • To assess the impact of KCTD12 on cancer cell migration and drug resistance.

Main Methods:

  • Ectopic expression of KCTD12 in the KYSE30 ESCC cell line.
  • Quantitative real-time PCR to analyze gene expression of stem cell factors, WNT/NOTCH pathway components, and chromatin remodelers.
  • Cell migration assays and 5-fluorouracil (5FU) resistance assays.

Main Results:

  • KCTD12 significantly downregulated key stem cell factors (NANOG, SOX2, SALL4, KLF4), WNT/NOTCH pathway components (MAML1, PYGO2), and chromatin remodelers (BMI1, BRG1, MSI1, MEIS1).
  • Expression of other genes including EGFR, DIDO1, ABCC4, ABCG2, and CRIPTO1 was also reduced by KCTD12.
  • Ectopic KCTD12 expression led to decreased cell migration (p=0.02) and reduced resistance to 5FU (p=0.01).

Conclusions:

  • KCTD12 exerts an inhibitory effect in ESCC by suppressing WNT/NOTCH signaling, stem cell factors, and chromatin remodelers.
  • KCTD12 demonstrates potential as an effective therapeutic marker for esophageal squamous cell carcinoma.
  • Targeting KCTD12 may offer a novel strategy for ESCC treatment.
Keywords:
Chromatin remodelingEsophageal cancerNOTCHSelf-renewalStem cellWNT

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