Supplementary Figures S1-S10 from Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival
Year: 2023
Type: supplementary-materials
Abstract: Supplementary Figure S1 shows RB1 is synthetic lethal with multiple genes that regulate chromosomal segregation. Supplementary Figure S2 shows genetic inactivation of AURKB is synthetic lethal with RB1 loss in NCI-H82 cells. Supplementary Figure S3 shows pharmacological inhibition of Aurora B kinase is synthetic lethal with RB1 loss in NCI-H82 cells. Supplementary Figure S4 shows RB1 is synthetic lethal with AURKB in other SCLC and NSCLC cell lines. Supplementary Figure S5 shows RB1-/-, MYC unamplified cancer cell lines are sensitive to AZD2811. Supplementary Figure S6 shows RB1 is synthetic lethal with AURKB in breast cancer cell lines. Supplementary Figure S7 shows pRB loss exacerbates mitotic abnormalities caused by Aurora B kinase inhibition. Supplementary Figure S8 shows AZD2811 is well tolerated in mice at concentrations used in our efficacy studies. Supplementary Figure S9 shows AZD2811 inhibits Aurora B Kinase in vivo, induces polyploidy, apoptosis, and its anti-tumor effects are on-target. Supplementary Figure S10 shows MYC, MYCN, MYCL1 copy number variation, mRNA expression, and immunohistochemistry in SCLC PDX models.
Authors: Matthew G. Oser, Raquel Fonseca, Abhishek A. Chakraborty, Rachel Brough, Alexander Spektor, Rebecca B. Jennings, Abdallah Flaifel, Jesse S. Novak, Aditi Gulati, Elizabeth Buss, Scott T. Younger, Samuel K. McBrayer, Glenn S. Cowley, Dennis M. Bonal, Quang-De Nguyen, Laura Brulle-Soumare, Paula Taylor, Stefano Cairo, Colm J. Ryan, Elizabeth J. Pease, Kim Maratea, Jon Travers, David E. Root, Sabina Signoretti, David Pellman, Susan Ashton, Christopher J. Lord, Simon T. Barry, William G. Kaelin
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4362617228