TUBB3/bIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

bIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non–small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that bIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesionassociated tumor suppressor maspin was differentially regulated by bIII-tubulin. Functionally, bIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by bIII-tubulin in NSCLC cells. bIII-Tubulin blockage in vivo reduced tumor incidence and growth.Overall, ourfindings revealed howbIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of bIII-tubulin in tumorigenesis. Cancer Res; 75(2); 1–11. 2014 AACR.