The EphB4 Receptor Tyrosine Kinase Promotes Lung Cancer Growth: A Potential Novel Therapeutic Target
Creators
- Ferguson, Benjamin D.1
- Liu, Ren2
- Rolle, Cleo E.1
- Tan, Yi-Hung Carol1
- Krasnoperov, Valery3
- Kanteti, Rajani1
- Tretiakova, Maria S.1
- Cervantes, Gustavo M.1
- Hasina, Rifat1
- Hseu, Robyn D.1
- Iafrate, A. John4
- Karrison, Theodore1
- Ferguson, Mark K.1
- Husain, Aliya N.1
- Faoro, Leonardo1
- Vokes, Everett E.1
- Gill, Parkash S.2
- Salgia, Ravi1
- 1. University of Chicago
- 2. University of Southern California
- 3. Vasgene Therapeutics, Inc.
- 4. Massachusetts General Hospital
Description
Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.
Files
journal.pone.0067668.pdf
Files
(26.0 MB)
| Name | Size | Download all |
|---|---|---|
|
Article md5:b38f78f4ba27d2293230499a2c1a7fe1 |
3.1 MB | Preview Download |
|
md5:b15a9bda41f799f7bc03f675c5f25afd
|
22.9 MB | Preview Download |
Additional details
Identifiers
- DOI
- 10.1371/journal.pone.0067668
- Other
- oai:uchicago.tind.io:10553
Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Graduate Training in Growth and Development
- ASCO
- Translational Award
- National Cancer Institute
- R01 CA 129501 05
- Janice Lamb McArdle Cancer Research Foundation