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
β1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy
Iris Eke, … , Veit Sandfort, Nils Cordes
Iris Eke, … , Veit Sandfort, Nils Cordes
Published March 1, 2012
Citation Information: J Clin Invest. 2012;122(4):1529-1540. https://doi.org/10.1172/JCI61350.
View: Text | PDF
Research Article Oncology Article has an altmetric score of 2

β1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy

  • Text
  • PDF
Abstract

Integrin signaling critically contributes to the progression, growth, and therapy resistance of malignant tumors. Here, we show that targeting of β1 integrins with inhibitory antibodies enhances the sensitivity to ionizing radiation and delays the growth of human head and neck squamous cell carcinoma cell lines in 3D cell culture and in xenografted mice. Mechanistically, dephosphorylation of focal adhesion kinase (FAK) upon inhibition of β1 integrin resulted in dissociation of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling and induced cell rounding, leading to radiosensitization. Thus, these findings suggest that robust and selective pharmacological targeting of β1 integrins may provide therapeutic benefit to overcome tumor cell resistance to radiotherapy.

Authors

Iris Eke, Yvonne Deuse, Stephanie Hehlgans, Kristin Gurtner, Mechthild Krause, Michael Baumann, Anna Shevchenko, Veit Sandfort, Nils Cordes

×

Figure 3

FAK-cortactin dispersion is essential for cell rounding and enhanced radiosensitivity.

Options: View larger image (or click on image) Download as PowerPoint
FAK-cortactin dispersion is essential for cell rounding and enhanced rad...
(A) Scheme of FAKwt-GFP, FAKca-GFP (K→E plus K→E at residues 578 and 581 [K578E/K581E]), and GFP empty vector controls (pEGFP-N1). (B) Western blot from whole cell lysates of UTSCC15 cells stably transfected with FAK-GFP fusion constructs indicated in A. β-Actin served as loading control. (C) Clonogenic survival of AIIB2-treated FAKca-GFP, FAKwt-GFP, and GFP transfectants (IgG#1 as control). Results show mean ± SD (n = 3; t test; **P < 0.01). (D) PLA using anti–β1 integrin and anti–FAK Y397 antibodies and confocal microscopy on AIIB2-treated UTSCC15 transfectants. DAPI was used for nuclear staining. Scale bar: 10 μm. (E) Clonogenic radiation survival of AIIB2-pretreated and irradiated (2–6 Gy) FAKca-GFP, FAKwt-GFP, and GFP transfectants. Results show mean ± SD (n = 3; t test; *P < 0.05; **P < 0.01). See also Supplemental Figure 15.

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

Sign up for email alerts

Posted by 2 X users
On 1 Facebook pages
158 readers on Mendeley
See more details