Supplementary Figures 1-8 from Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies in Lung Cancer by Suppressing BIM
Year: 2023
Type: supplementary-materials
Abstract: We have developed several models of EMT-mediated resistance to EGFR inhibitors in EGFR mutant lung cancers. Figure S1. Expression of EMT-related genes are inversely correlated with BCL2L11 expression; Figure S2. EMT induced by TGF-β results in depressed BIM and apoptotic resistance to EGFR inhibitors in EGFR mutant lung cancer. Figure S3. EGFRi resistant models that underwent an EMT have suppressed BIM levels. Figure S4. ZEB1 binding site located within the BCL2L11 (BIM) promoter. Figure S5. ZEB1 is an EMT marker associated with resistance to EGFRi in lung cancer and its depletion leads to BIM de-repression. Figure S6. BIM can be liberated with BCL-xL inhibition in mesenchymal EGFR mutant lung cancers to restore EGFRi-induced apoptosis. Figure S7. ABT-263 + EGFRi treatment is effective in EGFRi resistant cancers that have undergone an EMT. Figure S8. ER-TWIST phenotype in vivo and mesenchymal KRAS mutant lung cancers downregulate BIM upon EMT induction.
Authors: Kyung-A Song, Matthew J. Niederst, Timothy L. Lochmann, Aaron N. Hata, Hidenori Kitai, Jungoh Ham, Konstantinos V. Floros, Mark A. Hicks, Haichuan Hu, Hillary E. Mulvey, Yotam Drier, Daniel A.R. Heisey, Mark T. Hughes, Neha U. Patel, Elizabeth L. Lockerman, Angel Garcia, Shawn Gillepsie, Hannah L. Archibald, Maria Gomez-Caraballo, Tara J. Nulton, Brad E. Windle, Zofia Piotrowska, Sinem E. Sahingur, Shirley M. Taylor, Mikhail Dozmorov, Lecia V. Sequist, Bradley Bernstein, Hiromichi Ebi, Jeffrey A. Engelman, Anthony C. Faber
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361920576