Activation of KIT signaling promotes early tumorigenesis through the AP-1 pathway in APC/TP53 double-knockout human

Related Experiment Video

Updated: Jul 6, 2026

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
05:21

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy

Published on: October 6, 2014

Younghee Choi1,2, Eunju Kim1,2, Soo-Yeon Cho2

  • 1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.

Cell Death & Disease
|July 4, 2026
PubMed

Insights

Simultaneous inactivation of APC and TP53 genes drives early colorectal cancer (CRC) by upregulating KIT. This novel AP-1/KIT signaling axis promotes tumor growth, offering new therapeutic targets for CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) involves progressive genetic mutations, frequently affecting APC and TP53.
  • Epigenetic mechanisms linking simultaneous APC and TP53 inactivation to tumorigenesis are not well understood.

Purpose of the Study:

  • To investigate the epigenetic landscape of early-stage CRC.
  • To identify key molecular drivers and signaling pathways involved in APC and TP53-driven colorectal tumorigenesis.

Main Methods:

  • Developed a human colon organoid model with CRISPR-Cas9 to knock out APC and TP53 genes.
  • Conducted multi-omics profiling to analyze epigenetic changes.
  • Performed functional analyses to assess the role of identified molecular targets.

Main Results:

  • Identified KIT, a receptor tyrosine kinase, as a critical oncogenic driver upregulated in APC and TP53 double knockout (ΔDKO) organoids.
  • Demonstrated that KIT activates MAPK and Wnt signaling pathways, promoting proliferation and tumorigenesis.
  • Revealed that AP-1 transcription factors (FOS/JUN) regulate KIT expression through chromatin remodeling.

Conclusions:

  • Discovered a novel AP-1/KIT signaling axis crucial for early CRC progression.
  • Established KIT as integral to sustaining high proliferation rates in early-stage CRC.
  • Highlighted the AP-1/KIT axis as a potential therapeutic target for colorectal cancer.

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