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Updated: Feb 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

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Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal

Marie Alexandra Albaret1,2, Claudine Vermot-Desroches3, Arnaud Paré4,5,6

  • 1Univ Lyon, Université Claude Bernard Lyon 1, INSERM U1052, CNRS UMR5286, Centre Léon Bérard, Cancer Research Center of Lyon, 69008 Lyon, France. marie.albaret@lyon.unicancer.fr.

Cancers
|November 21, 2018
PubMed

Insights

Externalized cytokeratin 8 (eK8) drives colorectal cancer growth by controlling apoptosis and invasion. A novel monoclonal antibody targeting eK8 shows promise for treating colorectal cancers, including KRAS-mutant types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cancer cells exhibit intracellular proteins on their surface, termed externalized proteins.
  • These externalized proteins are promising therapeutic targets, but their roles in cancer are poorly understood.
  • Externalized cytokeratin 8 (eK8) is implicated in colorectal cancer (CRC) progression.

Purpose of the Study:

  • To investigate the role of externalized cytokeratin 8 (eK8) in colorectal tumorigenesis.
  • To characterize the mechanism of action of eK8 in CRC.
  • To develop and evaluate a therapeutic antibody targeting eK8.

Main Methods:

  • Generation of a monoclonal antibody (D-A10 MAb) targeting a specific eK8 domain.
  • Assessment of eK8's pro-tumoral activity in KRAS-mutant and wild-type CRC models.
  • In vivo and in vitro studies to analyze eK8's impact on apoptosis and cell invasion.

Main Results:

  • eK8 promotes colorectal tumorigenesis through bidirectional control of apoptosis and plasminogen-induced invasion.
  • eK8 is anchored to the plasma membrane, mediating these dual functions.
  • The D-A10 MAb targeting eK8 demonstrated anti-neoplastic activity in CRC models.

Conclusions:

  • Externalized cytokeratin 8 (eK8) is a key driver of colorectal tumorigenesis.
  • eK8 represents an innovative therapeutic target for CRC.
  • A novel monoclonal antibody targeting eK8 shows potential for treating CRC, including KRAS-mutant forms.
Keywords:
KRAS-mutant colorectal cancerbidirectional signalingexternalized keratin 8monoclonal antibodytherapeutic target

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