دورية أكاديمية
Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers.
| العنوان: | Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers. |
|---|---|
| المؤلفون: | Williams MM; Program in Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA., Elion DL; Program in Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA., Rahman B; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA., Hicks DJ; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA., Sanchez V; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Cook RS; Program in Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.; Department of Biomedical Engineering, Vanderbilt University, Nashville TN 37232, USA.; The Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. |
| المصدر: | Oncotarget [Oncotarget] 2019 Oct 09; Vol. 10 (52), pp. 5389-5402. Date of Electronic Publication: 2019 Oct 09 (Print Publication: 2019). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
| مستخلص: | Cancers often overexpress anti-apoptotic Bcl-2 proteins for cell death evasion, a recognized hallmark of cancer progression. While estrogen receptor (ER)-α+ breast cancers express high levels of three anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1), pharmacological inhibition of Bcl-2 and/or Bcl-xL fails to induce cell death in ERα+ breast cancer cell lines, due to rapid and robust Mcl-1 upregulation. The mechanisms of acute Mcl-1 upregulation in response to Bcl-2/Bcl-xL inhibition remain undefined in in ERα+ breast cancers. We report here that blockade of Bcl-2 or Bcl-xL, alone or together, rapidly induced mTOR signaling in ERα+ breast cancer cells, rapidly increasing cap-dependent Mcl-1 translation. Cells treated with a pharmacological inhibitor of cap-dependent translation, or with the mTORC1 inhibitor RAD001/everolimus, displayed reduced protein levels of Mcl-1 under basal conditions, and failed to upregulate Mcl-1 protein expression following treatment with ABT-263, a pharmacological inhibitor of Bcl-2 and Bcl-xL. Although treatment with ABT-263 alone did not sustain apoptosis in tumor cells in culture or in vivo , ABT-263 plus RAD001 increased apoptosis to a greater extent than either agent used alone. Similarly, combined use of the selective Mcl-1 inhibitor VU661013 with ABT-263 resulted in tumor cell apoptosis and diminished tumor growth in vivo . These findings suggest that rapid Mcl-1 translation drives ABT-263 resistance, but can be combated directly using emerging Mcl-1 inhibitors, or indirectly through existing and approved mTOR inhibitors. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest in the performance, analysis, or presentation of experiments and resulting data herein. This manuscript and all information herein is not under consideration for publication elsewhere. (Copyright: © 2019 Williams et al.) |
| References: | Cancer Res. 2014 May 15;74(10):2846-56. (PMID: 24614082) Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10853-8. (PMID: 18664580) Clin Cancer Res. 2013 Jun 15;19(12):3212-23. (PMID: 23633452) Nature. 2016 Oct 27;538(7626):477-482. (PMID: 27760111) Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1046-51. (PMID: 21191102) Cell Death Dis. 2018 Jan 17;9(2):21. (PMID: 29343814) Transplantation. 1997 Jul 15;64(1):32-5. (PMID: 9233697) ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93. (PMID: 25313317) Nat Med. 2013 Feb;19(2):202-8. (PMID: 23291630) Sci Transl Med. 2016 Dec 14;8(369):369ra175. (PMID: 27974663) J Exp Med. 2011 Aug 29;208(9):1799-807. (PMID: 21859846) Cancer Cell. 2013 Jul 8;24(1):120-9. (PMID: 23845444) Genes Dev. 2005 Jun 1;19(11):1294-305. (PMID: 15901672) J Clin Invest. 2014 Nov;124(11):4737-52. (PMID: 25250573) Cancer Discov. 2018 Dec;8(12):1566-1581. (PMID: 30185627) Lancet Oncol. 2010 Dec;11(12):1149-59. (PMID: 21094089) Cancer Lett. 2014 Jun 28;348(1-2):38-49. (PMID: 24650799) Oncotarget. 2015 Feb 28;6(6):3519-30. (PMID: 25784482) J Cell Sci. 2014 Feb 15;127(Pt 4):788-800. (PMID: 24363449) Mol Cancer Res. 2017 Mar;15(3):259-268. (PMID: 28039357) Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1288-96. (PMID: 25737542) Cancer Res. 2007 May 15;67(10):4564-71. (PMID: 17495324) J Clin Invest. 2013 Oct;123(10):4329-43. (PMID: 23999432) Front Oncol. 2018 Aug 10;8:308. (PMID: 30148117) BMC Cancer. 2015 May 29;15:442. (PMID: 26021831) FEBS Lett. 2017 Jan;591(1):240-251. (PMID: 27878989) Oncogene. 2016 Apr 14;35(15):1877-87. (PMID: 26257067) Cancer Discov. 2014 Jan;4(1):42-52. (PMID: 24163374) J Med Chem. 2019 Apr 25;62(8):3971-3988. (PMID: 30929420) Mol Cancer Ther. 2015 Aug;14(8):1837-47. (PMID: 26013319) Nat Rev Cancer. 2010 Apr;10(4):254-66. (PMID: 20332778) Genesis. 2006 Oct;44(10):477-86. (PMID: 16991114) J Biol Chem. 2013 Dec 6;288(49):35287-96. (PMID: 24133218) J Mammary Gland Biol Neoplasia. 2006 Jan;11(1):53-61. (PMID: 16900391) Br J Pharmacol. 2014 Aug;171(16):3801-13. (PMID: 24780124) Oncotarget. 2014 Dec 15;5(23):11778-91. (PMID: 25473892) Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2766-71. (PMID: 21768359) Cancer J Sci Am. 1997 Jul-Aug;3(4):230-7. (PMID: 9263629) ACS Med Chem Lett. 2015 Jun 22;6(8):948-52. (PMID: 26288699) J Clin Oncol. 2012 Feb 10;30(5):488-96. (PMID: 22184378) Cell Death Differ. 2008 Jun;15(6):977-87. (PMID: 18369371) Breast Cancer Res Treat. 2019 Feb;173(3):585-596. (PMID: 30374681) Mol Cell. 2001 Sep;8(3):705-11. (PMID: 11583631) Br J Cancer. 2010 Aug 24;103(5):668-75. (PMID: 20664598) Oncogene. 2008 Oct 27;27(50):6398-406. (PMID: 18955968) Mol Biol Int. 2014;2014:686984. (PMID: 25505994) |
| معلومات مُعتمدة: | F31 CA195989 United States CA NCI NIH HHS; R25 GM062459 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: ABT-263 resistance; Mcl-1; luminal breast cancers; mTORC1 signaling |
| تواريخ الأحداث: | Date Created: 20191010 Latest Revision: 20200831 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6739218 |
| DOI: | 10.18632/oncotarget.27070 |
| PMID: | 31595181 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1949-2553 |
|---|---|
| DOI: | 10.18632/oncotarget.27070 |