- No file added yet -

Figure S1-S16 from Expression of Neuroendocrine Factor VGF in Lung Cancer Cells Confers Resistance to EGFR Kinase Inhibitors and Triggers Epithelial-to-Mesenchymal Transition

figure

posted on 2023-03-31, 00:31 authored by Wen Hwang, Yu-Fan Chiu, Ming-Han Kuo, Kuan-Lin Lee, An-Chun Lee, Chia-Cherng Yu, Junn-Liang Chang, Wen-Chien Huang, Shih-Hsin Hsiao, Sey-En Lin, Yu-Ting Chou

'Figure S1. Lack of T790M and amplification of MET in HCC827GR cells; Figure S2. VGF-expressing cells are resistant to rociletinib; Figure S3. VGF expression in neuroendocrine carcinoma and EGFR-TKI resistant cells; Figure S4. VGF is expressed in the independently selected EGFR-TKI resistant HCC827 pool; Figure S5. Correlation of VGF levels with EGFR-TKI resistance and EMT in EGFR-TKI selected single cell clones; Figure S6. Effect of VGF expression on cell survival; Figure S7. VGF is highly expressed in small cell lung cancer; Figure S8. VGF is highly expressed in large cell neuroendocrine carcinoma; Figure S9. Correlation of VGF, CEACAM6, SYP, and CHGB expression levels with IC50 values of gefitinib in EGFR-mutated lung cancer cell lines; Figure S10. EGFR-TKI resistance in H1975 cells expressing differential VGF levels; Figure S11. VGF-TWIST1 signaling encourages EGFR-TKI resistance; Figure S12. Effect of conditioned medium from VGF expressing cells on low serum-mediated growth; Figure S13. Effect of doxycycline alone on tumor cell growth in vitro and in vivo; Figure S14. Correlation of VGF with EMT markers in lung adenocarcinoma; Figure S15. Correlation of neuroendocrine markers or TWIST1 with survival in lung adenocarcinoma; Figure S16. Correlation of neuroendocrine markers or VGF-TWIST1 signature with survival in EGFR-mutated lung adenocarcinoma.'

Funding

National Tsing Hua University

SMOBiO Inc

History

ARTICLE ABSTRACT

Mutations in EGFR drive tumor growth but render tumor cells sensitive to treatment with EGFR tyrosine kinase inhibitors (TKI). Phenotypic alteration in epithelial-to-mesenchymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma. However, the mechanism underlying this resistance remains unclear. Here we report that high expression of a neuroendocrine factor termed VGF induces the transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subset of lung adenocarcinoma cells. VGF silencing resensitized EGFR-mutated lung adenocarcinoma cells to TKI. Conversely, overexpression of VGF in sensitive cells conferred resistance to TKIs and induced EMT, increasing migratory and invasive behaviors. Correlation analysis revealed a significant association of VGF expression with advanced tumor grade and poor survival in patients with lung adenocarcinoma. In a mouse xenograft model of lung adenocarcinoma, suppressing VGF expression was sufficient to attenuate tumor growth. Overall, our findings show how VGF can confer TKI resistance and trigger EMT, suggesting its potential utility as a biomarker and therapeutic target in lung adenocarcinoma. Cancer Res; 77(11); 3013–26. ©2017 AACR.