Related Experiment Video

Updated: Jun 23, 2026

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
08:14

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

Published on: October 26, 2018

CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells

Yaohe Wang1, Rathi Gangeswaran, Xingbo Zhao

  • 1Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, London, United Kingdom. yaohe.wang@cancer.org.uk

The Journal of Clinical Investigation
|May 5, 2009
PubMed

Insights

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) hinders adenovirus cancer therapy by blocking viral entry and replication. Targeting CEACAM6 or its pathways may improve oncolytic adenovirus efficacy and predict patient response.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Tumorigenesis alters cancer cell surface molecules and signaling pathways, reducing adenovirus-based therapy effectiveness.
  • Adenovirus vector delivery is often inefficient due to cellular changes during cancer development.

Purpose of the Study:

  • To identify cellular factors restricting adenovirus infection in cancer cells.
  • To investigate the role of CEACAM6 in antagonizing adenovirus entry and replication.
  • To explore CEACAM6 and associated pathways as therapeutic targets for improving oncolytic adenovirus efficacy.

Main Methods:

  • Identified CEACAM6 as a protein restricting adenovirus infection.
  • Demonstrated CEACAM6's antagonism of the Src signaling pathway and its effect on cytoskeleton proteins.
  • Assessed the impact of CEACAM6 knockdown and Src inhibition on adenovirus replication and therapeutic effects in vitro and in vivo mouse xenograft models.

Main Results:

  • CEACAM6 was identified as a key inhibitor of adenovirus infection in human pancreatic cancer cells.
  • CEACAM6 antagonizes Src signaling, downregulates cytoskeleton proteins, and blocks nuclear adenovirus trafficking.
  • Src inhibition and CEACAM6 knockdown significantly enhanced adenovirus replication and antitumor effects in preclinical models.

Conclusions:

  • CEACAM6 restricts adenovirus-based cancer therapy by interfering with viral entry and nuclear transport.
  • Targeting CEACAM6 or Src signaling pathways presents a promising strategy for enhancing oncolytic adenovirus efficacy.
  • CEACAM6-associated pathways may serve as predictive biomarkers for patient response to adenovirus therapies.

More Related Videos

Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches13:36

Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches

Published on: May 6, 2015

Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts11:00

Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts

Published on: September 9, 2010

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...