betaIII-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. betaIII-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 betaIII-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of betaIII-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that betaIII-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. betaIII-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.
McCarroll
Joshua A
JA
Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Randwick, New South Wales, Australia.
Gan
Pei Pei
PP
Liu
Marjorie
M
Kavallaris
Maria
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000502:physiology*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin; C462941:beta3 tubulin, mouse; D002945:Cisplatin