Related Experiment Video

Updated: Jun 2, 2026

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
10:33

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts

Published on: April 29, 2014

KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis

Dawei Li1, Zhihai Peng, Huamei Tang

  • 1Departments of General Surgery and Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, PR China.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 3, 2011
PubMed
Abstract

Insights

Interferon-induced transmembrane protein 3 (IFITM3) is overexpressed in colorectal cancer, promoting tumor growth and metastasis. Loss of tumor suppressor KLF4 leads to increased IFITM3, driving colon cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-inducible gene.
  • IFITM3 is known to be overexpressed in various human cancers, including colorectal cancer.
  • The precise role and regulatory mechanisms of IFITM3 in colon tumorigenesis require further elucidation.

Purpose of the Study:

  • To investigate the clinical significance of IFITM3 dysregulation in human colon cancer.
  • To elucidate the underlying molecular mechanisms driving IFITM3 overexpression in colorectal cancer.
  • To evaluate the impact of IFITM3 on tumor progression and metastasis in both human specimens and preclinical models.

Main Methods:

  • Immunohistochemical analysis of IFITM3 expression in 203 patient colon tumor and matched normal tissue specimens, including lymph node metastases.
  • In vitro studies using siRNA to knockdown IFITM3 in colon cancer cells, assessing proliferation, colony formation, migration, and invasion.
  • In vivo studies using a xenograft model to evaluate the effect of IFITM3 knockdown on tumor growth and metastasis.
  • Chromatin immunoprecipitation and promoter mutagenesis assays to determine KLF4 binding to the IFITM3 promoter.
  • Analysis of IFITM3 and KLF4 expression in a conditional knockout murine model (Villin-Cre(+);Klf4(fl/fl)).

Main Results:

  • IFITM3 expression was significantly elevated in colon tumors and lymph node metastases compared to normal colon tissue.
  • High IFITM3 expression independently predicted poorer disease-free survival in colon cancer patients.
  • IFITM3 knockdown suppressed colon cancer cell proliferation, migration, invasion, and reduced tumor growth and metastasis in vivo.
  • Restored KLF4 expression downregulated IFITM3, while KLF4 deletion led to IFITM3 overexpression.
  • An inverse correlation between KLF4 loss and IFITM3 overexpression was observed in human colon tumors.

Conclusions:

  • IFITM3 is a direct transcriptional target of the tumor suppressor KLF4.
  • Dysregulated KLF4 expression results in aberrant IFITM3 overexpression.
  • Aberrant IFITM3 expression contributes to the progression and metastasis of colorectal cancer.

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