RESUMO
ßIII-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 ßIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesion-associated tumor suppressor maspin was differentially regulated by ßIII-tubulin. Functionally, ßIII-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 ßIII-tubulin in NSCLC cells. ßIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how ßIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of ßIII-tubulin in tumorigenesis.
