Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells
Yaohe Wang, … , Ziming Dong, Nick Lemoine
Yaohe Wang, … , Ziming Dong, Nick Lemoine
Published May 1, 2009
Citation Information: J Clin Invest. 2009;119(6):1604-1615. https://doi.org/10.1172/JCI37905.
View: Text | PDF
Research Article Oncology

CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells

  • Text
  • PDF
Abstract

The changes in cancer cell surface molecules and intracellular signaling pathways during tumorigenesis make delivery of adenovirus-based cancer therapies inefficient. Here we have identified carcinoembryonic antigen–related cell adhesion molecule 6 (CEACAM6) as a cellular protein that restricts the ability of adenoviral vectors to infect cancer cells. We have demonstrated that CEACAM6 can antagonize the Src signaling pathway, downregulate cancer cell cytoskeleton proteins, and block adenovirus trafficking to the nucleus of human pancreatic cancer cells. Similar to CEACAM6 overexpression, treatment with a Src-selective inhibitor significantly reduced adenovirus replication in these cancer cells and normal human epithelial cells. In a mouse xenograft tumor model, siRNA-mediated knockdown of CEACAM6 also significantly enhanced the antitumor effect of an oncolytic adenovirus. We propose that CEACAM6-associated signaling pathways could be potential targets for the development of biomarkers to predict the response of patients to adenovirus-based therapies, as well as for the development of more potent adenovirus-based therapeutics.

Authors

Yaohe Wang, Rathi Gangeswaran, Xingbo Zhao, Pengju Wang, James Tysome, Vipul Bhakta, Ming Yuan, C.P. Chikkanna-Gowda, Guozhong Jiang, Dongling Gao, Fengyu Cao, Jennelle Francis, Jinxia Yu, Kangdong Liu, Hongyan Yang, Yunhan Zhang, Weidong Zang, Claude Chelala, Ziming Dong, Nick Lemoine

×

Figure 5

CEACAM6 interferes with adenovirus infection by altering cytoskeleton of cancer cells via the Src pathway.

Options: View larger image (or click on image) Download as PowerPoint
CEACAM6 interferes with adenovirus infection by altering cytoskeleton of...
(A) Confocal analysis showing the expression of F-actin, tubulin, and dynactin in PaTu8988t-Hyg, PaTu8988t-CEACAM6, and control siRNA–treated Suit-2 cells and in CEACAM6-specific SMARTpool siRNA–treated Suit-2 cells; original magnification, ×600. DAPI (blue) indicates nuclei; green indicates CEACAM6; and red indicates F-actin, tubulin, or dynactin. (B) Western blot analysis showing the expression of tubulin and dynactin. (C) Western blot analysis showing the expression of CEACAM6, Src-529, Src-418, and pan-Src. (D) c-Src kinase activity in stable clones PaTu8988t-Hyg and PaTu8988t-CEACAM6. (E) Western blot analysis showing the expression of Src-418 and pan-Src in untreated and PP2-treated PaTu8988t cells. (F) Confocal analysis showing the expression of F-actin, tubulin, and dynactin in untreated and PP2-treated PaTu8988t cells; original magnification, ×600. (G) Cell killing assays with different MOI of adenovirus in untreated and PP2-pretreated PaTu8988t cells. (H) Adenovirus replication in untreated and PP2-pretreated PaTu8988t cells. (I) Adenovirus replication in untreated and PP2-pretreated normal human bronchial epithelial (NHBE) cells. All experiments were repeated at least 3 times. *P < 0.05, **P < 0.01, ***P < 0.001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts