Supplementary Figure 7 from TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

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posted on 2023-03-30, 23:02 authored by Joshua A. McCarroll, Pei Pei Gan, Rafael B. Erlich, Marjorie Liu, Tanya Dwarte, Sharon S. Sagnella, Mia C. Akerfeldt, Lu Yang, Amelia L. Parker, Melissa H. Chang, Michael S. Shum, Frances L. Byrne, Maria Kavallaris

A) A graph showing a decrease in ÃŽÂ²III-tubulin mRNA expression in A549 NSCLC cells stably expressing ÃŽÂ²III-tubulin shRNA (pRS/ÃŽÂ²IIISH61) vs. cells stably expressing control shRNA (pRS/CtrlSH27). B) Representative western blot demonstrating potent knockdown of ÃŽÂ²III-tubulin protein expression in A549 NSCLC cells stably expressing ÃŽÂ²III-tubulin shRNA (pRS/ÃŽÂ²IIISH61) vs. cells stably expressing control shRNA (pRS/CtrlSH27). GAPDH was used a protein loading control, n = 3 experiments.

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ARTICLE ABSTRACT

βIII-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 βIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesion-associated tumor suppressor maspin was differentially regulated by βIII-tubulin. Functionally, βIII-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 βIII-tubulin in NSCLC cells. βIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how βIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of βIII-tubulin in tumorigenesis. Cancer Res; 75(2); 415–25. ©2014 AACR.