Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures

  • Authors:
    • Lydia Rossow
    • Iris Eke
    • Ellen Dickreuter
    • Nils Cordes
  • View Affiliations

  • Published online on: May 25, 2015     https://doi.org/10.3892/or.2015.4006
  • Pages: 469-476
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Epidermal growth factor receptor (EGFR) signaling plays an important role in tumor cell resistance to therapy. In addition to ligand binding, mutual and cooperative interactions of EGFR with integrin cell adhesion receptors critically influence proper downstream signaling through a number of bridging adapter proteins. In the present study, we analyzed the role of two of these adapter proteins, called PINCH1 and Nck2, for cellular radioresistance in combination with EGFR-targeting using the monoclonal antibody cetuximab. siRNA-mediated knockdown of PINCH1 or Nck2 resulted in enhanced radiosensitivity of 3D grown human squamous cell carcinoma cell lines FaDu (head and neck) and A431 (epidermis) comparable with effects seen after cetuximab treatment. Combination of knockdown and cetuximab did not result in additive nor synergistic effects regarding clonogenic radiation survival. Modifications in MAPK, Akt and FAK phosphorylation occurred upon cetuximab treatment as well as PINCH1 or Nck2 depletion. We further found this tumor cell radiosensitization to be due to attenuated repair of DNA double strand breaks and altered Rad50 and Nbs1 expression but without changes in other DNA repair proteins such as ATM, DNA-PK and Mre11. Our data suggest that the adaptor proteins PINCH1 and Nck2 critically contribute to cellular radioresistance and proper EGFR signaling in 3D lrECM grown human squamous cell carcinoma cells. Further investigations are warranted to identify the intracellular signaling network controlled by EGFR, PINCH1 and Nck2.
View Figures
View References

Related Articles

Journal Cover

July-2015
Volume 34 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Rossow L, Eke I, Dickreuter E and Cordes N: Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures. Oncol Rep 34: 469-476, 2015
APA
Rossow, L., Eke, I., Dickreuter, E., & Cordes, N. (2015). Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures. Oncology Reports, 34, 469-476. https://doi.org/10.3892/or.2015.4006
MLA
Rossow, L., Eke, I., Dickreuter, E., Cordes, N."Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures". Oncology Reports 34.1 (2015): 469-476.
Chicago
Rossow, L., Eke, I., Dickreuter, E., Cordes, N."Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures". Oncology Reports 34, no. 1 (2015): 469-476. https://doi.org/10.3892/or.2015.4006