Conformational Dynamics Allows Sampling of an "Active-like" State by Oncogenic K-Ras-GDP

Ma X, Bi E, Lu Y, Su P, Huang C, Liu L, et al. Cholesterol induces CD8+ T cell exhaustion in the tumor microenvironment. Cell Metab 2019;30:143-156.e5. https://doi.org/10.1016/j.cmet.2019.04.002. Goossens P, Rodriguez-Vita J, Etzerodt A, Masse M, Rastoin O, Gouirand V, et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab 2019;29:1376-1389.e4. https://doi.org/10.1016/j.cmet.2019.02.016. Li J, Liu J, Liang Z, He F, Yang L, Li P, et al. Simvastatin and atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth. Cell Death Dis 2017;8:1-12. https://doi.org/10.1038/ cddis.2017.46. Sehdev A, Shih YACT, Huo D, Vekhter B, Lyttle C, Polite B. The role of statins for primary prevention in non-elderly colorectal cancer patients. Anticancer Res 2014;34:5043-50. https://doi.org/10.1200/jco.2013.31.15_suppl.1513. Gray RT, Loughrey MB, Bankhead P, Cardwell CR, McQuaid S, O'Neill RF, et al. Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study. Br J Cancer 2017;116:1652-9. https://doi.org/10.1038/bjc.2017.139. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci 2005;102:15545-50. https://doi.org/10.1073/pnas.0506580102. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics 2011. https:// doi.org/10.1093/bioinformatics/btr260. Franz M, Rodriguez H, Lopes C, Zuberi K, Montojo J, Bader GD, et al. GeneMANIA update 2018. Nucleic Acids Res 2018;46. https://doi.org/ 10.1093/nar/gky311. W60-W64. D s, al g, d l, a j, s w, j h-c, m s, nt d, jh m, p b, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets Nucleic Acids Res 2019 47: [36] Wu T, Tian J, Cutler RG, Telljohann RS, Bernlohr DA, Mattson MP, et al. Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100secretion and triglyceride accumulation ARPE-19 cells. Lab Investig 2010;90:906-14. https://doi.org/10.1038/ labinvest.2009.33. [37] Furuhashi M, Ogura M, Matsumoto M, Yuda S, Muranaka A, Kawamukai M, et al. Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages. Sci Rep 2017;7:1-10. https://doi.org/10.1038/s41598-017-00177-w. [38] Pan L, Xiao H, Liao R, Chen Q, Peng C, Zhang Y, et al. Biomedicine & Pharmacotherapy Fatty acid binding protein 5 promotes tumor angiogenesis and activates the IL6 / STAT3 / VEGFA pathway in hepatocellular carcinoma. Biomed Pharmacother 2018;106:68-76. https://doi.org/10.1016/j. biopha.2018.06.040. [39] Mussunoor S, Murray GI. The role of annexins in tumour development and progression. (2008)131-140. doi:10.1002/path [40] Shen Y, Xiong W, Gu Q, Zhang Q, Yue J, Liu C, Wang D. Multi-Omics Integrative Analysis Uncovers Molecular Subtypes and mRNAs as Therapeutic Targets for Liver Cancer. (2021) 8:1-13. doi:10.3389/fmed.2021.654635. [41] Kitamura K, Okada Y, Okada K, Kawaguchi Y, Nagaoka S. Epigallocatechin gallate induces an up-regulation of LDL receptor accompanied by a reduction of PCSK9 via the annexin A2-independent pathway in HepG2 cells. Mol Nutr Food Res 2017;61:1-12. https://doi.org/10.1002/mnfr.201600836. [42] Shafqat N, Turnbull A, Zschocke J, Oppermann U, Yue WW. Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. J Mol Biol 2010;398:497-506. https://doi.org/10.1016/j.jmb.2010.03.034. [43] Puchalska P, Crawford PA. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab 2017;25:262-84. https:// doi.org/10.1016/j.cmet.2016.12.022.