βIII-Tubulin Is a Multifunctional Protein Involved in Drug Sensitivity and Tumorigenesis in Non-Small Cell Lung Cancer

Advanced non-small cell lung cancer (NSCLC) has a dismal prognosis. beta III-Tubulin, a protein highly expressed in neuronal cells, is strongly associated with drug-refractory and aggressive NSCLC. To date, the role of this protein in in vivo drug resistance and tumorigenesis has not been determined. NSCLC cells stably expressing beta III-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of beta III-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that beta III-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. beta III-Tubulin is a cellular survival factor that, when suppressed, sensitizes cells to chemotherapy via enhanced apoptosis induction and decreased tumorigenesis. Findings establish that upregulation of a neuronal tubulin isotype is a key contributor to tumor progression and drug sensitivity in lung adenocarcinoma. Cancer Res; 70(12); 4995-5003. (C)2010 AACR.