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Published on: February 20, 2017
EphrinB1: novel microtubule associated protein whose expression affects taxane sensitivity
Paul L Colbert1, Daniel W Vermeer1, Bryant G Wieking1
1Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
EphrinB1 binds microtubules (MTs) and influences taxane response. Human papillomavirus (HPV) infection alters EphrinB1, potentially predicting cancer treatment sensitivity.
Area of Science:
- Cell Biology
- Molecular Oncology
Background:
- Microtubules (MTs) are crucial for cell division and homeostasis.
- PTPN13 phosphatase is involved in mitosis and degraded by HPV16 E6.
- HPV infection's impact on cellular proliferation via PTPN13 substrates is unknown.
Purpose of the Study:
- Investigate if HPV affects EphrinB1 localization during mitosis.
- Determine EphrinB1's role as a microtubule-associated protein (MAP).
- Assess EphrinB1's impact on taxane response in HPV-infected cells.
Main Methods:
- Cell cycle analysis of EphrinB1 localization.
- Tubulin binding assays for phosphorylated and unphosphorylated EphrinB1.
- In vitro taxane response assays with HPV16 E6 expression.
Main Results:
- EphrinB1 co-localizes with MTs throughout the cell cycle.
- A cleaved, unphosphorylated EphrinB1 fragment binds tubulin.
- HPV16 E6 expression alters EphrinB1's effect on taxane response.
Conclusions:
- EphrinB1 is a novel MAP, binding tubulin in an unphosphorylated state.
- PTPN13 likely modulates EphrinB1 phosphorylation, affecting taxane sensitivity.
- EphrinB1 may predict taxane sensitivity in epithelial cancers, especially with HPV infection or PTPN13 mutations.
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