Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells

E. Zaganjor, J. K. Osborne, L. M. Weil, L. A. Diaz-Martinez, J. X. Gonzales, S. M. Singel, J. E. Larsen, L. Girard, J. D. Minna, M. H. Cobb

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Abstract

We show that expression of the microtubule depolymerizing kinesin KIF2C is induced by transformation of immortalized human bronchial epithelial cells (HBEC) by expression of K-Ras(G12V) and knockdown of p53. Further investigation demonstrates that this is due to the K-Ras/ERK1/2 MAPK pathway, as loss of p53 had little effect on KIF2C expression. In addition to KIF2C, we also found that the related kinesin KIF2A is modestly upregulated in this model system; both proteins are expressed more highly in many lung cancer cell lines compared to normal tissue. As a consequence of their depolymerizing activity, these kinesins increase dynamic instability of microtubules. Depletion of either of these kinesins impairs the ability of cells transformed with mutant K-Ras to migrate and invade matrigel. However, depletion of these kinesins does not reverse the epithelial to mesenchymal transition (EMT) caused by mutant K-Ras. Our studies indicate that increased expression of microtubule destabilizing factors can occur during oncogenesis to support enhanced migration and invasion of tumor cells.

Original languageEnglish (US)
Pages (from-to)5457-5466
Number of pages10
JournalOncogene
Volume33
Issue number47
DOIs
Publication statusPublished - Nov 20 2014

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ASJC Scopus subject areas

  • Medicine(all)

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Zaganjor, E., Osborne, J. K., Weil, L. M., Diaz-Martinez, L. A., Gonzales, J. X., Singel, S. M., ... Cobb, M. H. (2014). Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells. Oncogene, 33(47), 5457-5466. https://doi.org/10.1038/onc.2013.486