Loss of p53 expression in cancer cells alters cell cycle response after inhibition of exportin-1 but does not prevent cell death

References

• la Cour T, Kiemer L, Molgaard A, et al. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel. 2004;17:527–536.
   PubMed Web of Science ®Google Scholar
• Senapedis WT, Baloglu E, Landesman Y. Clinical translation of nuclear export inhibitors in cancer. Semin Cancer Biol. 2014;27:74–86.
   PubMed Web of Science ®Google Scholar
• Turner JG, Dawson J, Sullivan DM. Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol. 2012;83:1021–1032.
   PubMed Web of Science ®Google Scholar
• Cheng Y, Holloway MP, Nguyen K, et al. XPO1 (CRM1) inhibition represses STAT3 activation to drive a survivin-dependent oncogenic switch in triple-negative breast cancer. Mol Cancer Ther. 2014;13:675–686.
   PubMed Web of Science ®Google Scholar
• Hill R, Rabb M, Madureira PA, et al. Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy. Cell Death Dis. 2013;4:e791.
   PubMed Web of Science ®Google Scholar
• Gizatullin F, Yao Y, Kung V, et al. The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function. Cancer Res. 2006;66:7668–7677.
   PubMed Web of Science ®Google Scholar
• Lukin DJ, Carvajal LA, Liu WJ, et al. p53 Promotes cell survival due to the reversibility of its cell-cycle checkpoints. Mol Cancer Res. 2015;13:16–28.
   PubMed Web of Science ®Google Scholar
• Neggers JE, Vercruysse T, Jacquemyn M, et al. Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing. Chem Biol. 2015;22:107–116.
   PubMedGoogle Scholar
• Nakayama R, Zhang YX, Czaplinski JT, et al. Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma. Oncotarget. 2016;7:16581–16592.
   PubMedGoogle Scholar
• Razak ARA, Soerensen MM, Mahipal A, et al. First-in-class, first-in-human phase I trial of KPT-330, a selective inhibitor of nuclear export (SINE) in patients (pts) with advanced solid tumors. J Clin Oncol 2013;31:15_suppl: abstr 2505-2505.
   Google Scholar
• Lassen UN, Soerensen MM, Kung AL, et al. A phase 2 study on efficacy, safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM). J Clin Oncol 2015;33:15_suppl: abstr 2044-2044.
   Web of Science ®Google Scholar
• Vassilev LT. Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle. 2004;3:419–421.
   PubMed Web of Science ®Google Scholar
• Marcus JM, Burke RT, DeSisto JA, et al. Longitudinal tracking of single live cancer cells to understand cell cycle effects of the nuclear export inhibitor, selinexor. Scientific Reports. 2015;5:14391.
   PubMed Web of Science ®Google Scholar
• Mendonca J, Sharma A, Kim HS, et al. Selective inhibitors of nuclear export (SINE) as novel therapeutics for prostate cancer. Oncotarget. 2014;5:6102–6112.
   PubMedGoogle Scholar
• Yoshimura M, Ishizawa J, Ruvolo V, et al. Induction of p53-mediated transcription and apoptosis by exportin-1 (XPO1) inhibition in mantle cell lymphoma. Cancer Sci. 2014;105:795–801.
   PubMed Web of Science ®Google Scholar
• Purvis JE, Karhohs KW, Mock C, et al. p53 dynamics control cell fate. Science. 2012;336:1440–1444.
   PubMed Web of Science ®Google Scholar
• Azmi AS, Aboukameel A, Bao B, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology. 2013;144:447–456.
   PubMed Web of Science ®Google Scholar
• Allen MA, Andrysik Z, Dengler VL, et al. Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms. eLife. 2014;3:e02200.
   PubMed Web of Science ®Google Scholar
• Feng FY, Zhang Y, Kothari V, et al. MDM2 Inhibition sensitizes prostate cancer cells to androgen ablation and radiotherapy in a p53-dependent manner. Neoplasia. 2016;18:213–222.
   PubMed Web of Science ®Google Scholar
• Lau LM, Nugent JK, Zhao X, et al. HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function. Oncogene. 2008;27:997–1003.
   PubMed Web of Science ®Google Scholar
• Carrillo AM, Hicks M, Khabele D, et al. Pharmacologically increasing Mdm2 inhibits DNA repair and cooperates with genotoxic agents to kill p53-Inactivated ovarian cancer cells. Mol Cancer Res. 2015;13:1197–1205.
   PubMed Web of Science ®Google Scholar
• Conradt L, Henrich A, Wirth M, et al. Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death. Int J Cancer. 2013;132:2248–2257.
   PubMed Web of Science ®Google Scholar
• Sakaue-Sawano A, Kurokawa H, Morimura T, et al. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 2008;132:487–498.
   PubMed Web of Science ®Google Scholar
• Garzon R, Savona M, Baz R, et al. A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Blood. 2017;129:3165–3174.
   PubMed Web of Science ®Google Scholar
• Walker CJ, Oaks JJ, Santhanam R, et al. Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias. Blood. 2013;122:3034–3044.
   PubMed Web of Science ®Google Scholar
• Chen C, Siegel D, Gutierrez M, et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom’s macroglobulinemia. Blood. 2018;131:855–863.
   Web of Science ®Google Scholar
• Gounder MM, Zer A, Tap WD, et al. Phase IB study of selinexor, a first-in-class inhibitor of nuclear export, in patients with advanced refractory bone or soft tissue sarcoma. J Clin Oncol. 2016;34:3166–3174.
   PubMed Web of Science ®Google Scholar
• Abdul Razak AR, Mau-Soerensen M, Gabrail NY, et al. First-in-Class, First-in-Human phase I study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors. J Clin Oncol. 2016;34:4142–4150.
   PubMed Web of Science ®Google Scholar
• Moran DM, Maki CG. Nutlin-3a induces cytoskeletal rearrangement and inhibits the migration and invasion capacity of p53 wild-type cancer cells. Mol Cancer Ther. 2010;9:895–905.
   PubMed Web of Science ®Google Scholar
• Wasielewski M, Elstrodt F, Klijn JG, et al. Thirteen new p53 gene mutants identified among 41 human breast cancer cell lines. Breast Cancer Res Treat. 2006;99:97–101.
   PubMed Web of Science ®Google Scholar
• Liu Y, Bodmer WF. Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines. Proc Natl Acad Sci U S A. 2006;103:976–981.
   PubMed Web of Science ®Google Scholar
• Chang BD, Xuan Y, Broude EV, et al. Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene. 1999;18:4808–4818.
   PubMed Web of Science ®Google Scholar
• Clewell RA, Sun B, Adeleye Y, et al. Profiling dose-dependent activation of p53-mediated signaling pathways by chemicals with distinct mechanisms of DNA damage. Toxicol Sci. 2014;142:56–73.
   PubMed Web of Science ®Google Scholar
• Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002;296:550–553.
   PubMed Web of Science ®Google Scholar
• Loewer A, Batchelor E, Gaglia G, et al. Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells. Cell. 2010;142:89–100.
   PubMed Web of Science ®Google Scholar
• Bunz F, Dutriaux A, Lengauer C, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998;282:1497–1501.
   PubMed Web of Science ®Google Scholar
• Lapalombella R, Sun Q, Williams K, et al. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood. 2012;120:4621–4634.
   PubMed Web of Science ®Google Scholar
• Yano S, Li S, Han Q, et al. Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity. Oncotarget. 2014;5:8729–8736.
   PubMed Web of Science ®Google Scholar
• Bozzi F, Conca E, Laurini E, et al. In vitro and in silico studies of MDM2/MDMX isoforms predict Nutlin-3A sensitivity in well/de-differentiated liposarcomas. Lab Invest. 2013;93:1232–1240.
   PubMed Web of Science ®Google Scholar
• Paek AL, Liu JC, Loewer A, et al. Cell-to-cell variation in p53 dynamics leads to fractional killing. Cell. 2016;165:631–642.
   PubMed Web of Science ®Google Scholar
• Van Maerken T, Rihani A, Van Goethem A, et al. Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer. Cancer Lett. 2014;344:157–165.
   PubMed Web of Science ®Google Scholar
• Henze J, Muhlenberg T, Simon S, et al. p53 modulation as a therapeutic strategy in gastrointestinal stromal tumors. PLoS One. 2012;7:e37776.
   PubMed Web of Science ®Google Scholar
• Barone G, Tweddle DA, Shohet JM, et al. MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance. Current Drug Targets. 2014;15:114–123.
   PubMed Web of Science ®Google Scholar
• Henderson BR, Eleftheriou A. A comparison of the activity, sequence specificity, and CRM1-dependence of different nuclear export signals. Exp Cell Res. 2000;256:213–224.
   PubMed Web of Science ®Google Scholar
• Lain S, Midgley C, Sparks A, et al. An inhibitor of nuclear export activates the p53 response and induces the localization of HDM2 and p53 to U1A-positive nuclear bodies associated with the PODs. Exp Cell Res. 1999;248:457–472.
   PubMed Web of Science ®Google Scholar
• Yang XH, Sladek TL, Liu X, et al. Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res. 2001;61:348–354.
   PubMed Web of Science ®Google Scholar
• Lin YF, Lai TC, Chang CK, et al. Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient malignancies. J Clin Invest. 2013;123:3861–3875.
   PubMed Web of Science ®Google Scholar
• Burke RT, Marcus JM, Orth JD. Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells. Oncotarget. 2017;8:39460–39475.
   PubMedGoogle Scholar
• Procopio MG, Laszlo C, Al Labban D, et al. Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation. Nat Cell Biol. 2015;17:1193–1204.
   PubMed Web of Science ®Google Scholar
• Nikkila J, Kumar R, Campbell J, et al. Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. Br J Cancer. 2017;117:113–123.
   PubMed Web of Science ®Google Scholar
• Gadagkar SR, Call GB. Computational tools for fitting the Hill equation to dose-response curves. J Pharmacol Toxicol Methods. 2015;71:68–76.
   PubMed Web of Science ®Google Scholar