دورية أكاديمية
أعرض في EDS

Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth.

التفاصيل البيبلوغرافية
العنوان: Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth.
المؤلفون: Penny MK; Doctoral Program in Cancer Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Lerario AM; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA., Basham KJ; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA., Chukkapalli S; Mott Solid Tumor Oncology Program, C.S. Mott Children's and Women's Hospital, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA., Mohan DR; Doctoral Program in Cancer Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA., LaPensee C; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA., Converso-Baran K; UMH Frankel Cardiovascular Center Physiology and Phenotyping Core, Ann Arbor, MI 48109, USA., Hoenerhoff MJ; In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Suárez-Fernández L; Department Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, 33011 Oviedo, Spain., Rey CGD; Department of Pathology, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, 33011 Oviedo, Spain., Giordano TJ; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.; Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109, USA., Han R; Iterion Therapeutics, Inc., Houston, TX 77021, USA., Newman EA; Mott Solid Tumor Oncology Program, C.S. Mott Children's and Women's Hospital, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA., Hammer GD; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.; Endocrine Oncology Program, Rogel Cancer Center, University of Michigan Health System, Ann Arbor, MI 48109, USA.
المصدر: Cancers [Cancers (Basel)] 2023 Jul 10; Vol. 15 (14). Date of Electronic Publication: 2023 Jul 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: Adrenocortical carcinoma (ACC) is a rare but highly aggressive cancer with limited treatment options and poor survival for patients with advanced disease. An improved understanding of the transcriptional programs engaged in ACC will help direct rational, targeted therapies. Whereas activating mutations in Wnt/β-catenin signaling are frequently observed, the β-catenin-dependent transcriptional targets that promote tumor progression are poorly understood. To address this question, we analyzed ACC transcriptome data and identified a novel Wnt/β-catenin-associated signature in ACC enriched for the extracellular matrix (ECM) and predictive of poor survival. This suggested an oncogenic role for Wnt/β-catenin in regulating the ACC microenvironment. We further investigated the minor fibrillar collagen, collagen XI alpha 1 (COL11A1), and found that COL11A1 expression originates specifically from cancer cells and is strongly correlated with both Wnt/β-catenin activation and poor patient survival. Inhibition of constitutively active Wnt/β-catenin signaling in the human ACC cell line, NCI-H295R, significantly reduced the expression of COL11A1 and other ECM components and decreased cancer cell viability. To investigate the preclinical potential of Wnt/β-catenin inhibition in the adrenal microenvironment, we developed a minimally invasive orthotopic xenograft model of ACC and demonstrated that treatment with the newly developed Wnt/β-catenin:TBL1 inhibitor Tegavivint significantly reduced tumor growth. Together, our data support that the inhibition of aberrantly active Wnt/β-catenin disrupts transcriptional reprogramming of the microenvironment and reduces ACC growth and survival. Furthermore, this β-catenin-dependent oncogenic program can be therapeutically targeted with a newly developed Wnt/β-catenin inhibitor. These results show promise for the further clinical development of Wnt/β-catenin inhibitors in ACC and unveil a novel Wnt/β-catenin-regulated transcriptome.
References: Cancer Cell. 2016 May 9;29(5):723-736. (PMID: 27165744)
Oncogene. 2020 Jul;39(30):5282-5291. (PMID: 32561853)
Nat Genet. 2001 May;28(1):53-7. (PMID: 11326276)
In Vivo. 2017 Sep-Oct;31(5):779-791. (PMID: 28882943)
Am J Surg Pathol. 1989 Mar;13(3):202-6. (PMID: 2919718)
J Biol Chem. 2002 Sep 6;277(36):33398-410. (PMID: 12052822)
Cancer Cell. 2004 Jan;5(1):91-102. (PMID: 14749129)
Nat Genet. 2014 Jun;46(6):607-12. (PMID: 24747642)
Mol Endocrinol. 2014 Sep;28(9):1471-86. (PMID: 25029241)
Cancer Lett. 2016 Nov 28;382(2):203-214. (PMID: 27609069)
Cancer Cell. 2022 Aug 8;40(8):818-834.e9. (PMID: 35868307)
Oncotarget. 2015 Sep 15;6(27):23748-63. (PMID: 26087191)
Nat Cell Biol. 2008 Feb;10(2):160-9. (PMID: 18193033)
Mol Cell Endocrinol. 2017 Apr 15;445:42-54. (PMID: 27940298)
Oncotarget. 2017 Apr 7;8(31):51050-51057. (PMID: 28881628)
Development. 2008 Aug;135(15):2593-602. (PMID: 18599507)
Cancer Res. 2005 Sep 1;65(17):7622-7. (PMID: 16140927)
Mol Cancer Ther. 2017 Sep;16(9):1765-1778. (PMID: 28500235)
Nat Rev Mol Cell Biol. 2014 Dec;15(12):786-801. (PMID: 25415508)
Endocr Rev. 2014 Apr;35(2):282-326. (PMID: 24423978)
Clin Cancer Res. 2011 Jan 15;17(2):328-36. (PMID: 21088256)
J Clin Endocrinol Metab. 2008 Aug;93(8):3222-5. (PMID: 18544621)
Bioinformatics. 2016 Sep 15;32(18):2847-9. (PMID: 27207943)
Nat Med. 2005 Nov;11(11):1156-9. (PMID: 16270068)
J Biol Chem. 2010 Apr 30;285(18):13507-16. (PMID: 20181957)
Nat Commun. 2020 Apr 3;11(1):1680. (PMID: 32245949)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
Carcinogenesis. 2005 Mar;26(3):513-23. (PMID: 15358632)
Hum Mol Genet. 2010 Apr 15;19(8):1561-76. (PMID: 20106872)
Mol Cell Proteomics. 2018 May;17(5):901-912. (PMID: 29386236)
Mol Cell Endocrinol. 2012 Nov 25;364(1-2):101-4. (PMID: 22960230)
Cell. 2012 Jun 8;149(6):1192-205. (PMID: 22682243)
Cancer Res. 2002 Oct 15;62(20):5651-6. (PMID: 12384519)
Science. 2018 Oct 26;362(6413):. (PMID: 30361341)
Leukemia. 2015 Jun;29(6):1267-78. (PMID: 25482131)
PLoS One. 2013;8(2):e55743. (PMID: 23409032)
Clin Cancer Res. 2014 Feb 1;20(3):711-23. (PMID: 24218511)
BMC Bioinformatics. 2013 Jan 16;14:7. (PMID: 23323831)
J Clin Endocrinol Metab. 2014 Feb;99(2):455-61. (PMID: 24302750)
Nucleic Acids Res. 2016 May 5;44(8):e71. (PMID: 26704973)
Mol Cell Endocrinol. 2016 Feb 5;421:28-33. (PMID: 26033247)
Genes Dev. 2019 Feb 1;33(3-4):209-220. (PMID: 30692207)
Cell Transplant. 2010;19(5):565-72. (PMID: 20525431)
Oncotarget. 2015 Dec 15;6(40):43016-32. (PMID: 26515592)
Oncotarget. 2017 May 10;8(39):65090-65099. (PMID: 29029414)
PLoS One. 2013 Oct 23;8(10):e78327. (PMID: 24194920)
J Natl Cancer Inst. 2019 Nov 1;111(11):1216-1227. (PMID: 30793158)
J Med Chem. 2015 Aug 13;58(15):5854-62. (PMID: 26182238)
Biomolecules. 2023 Jan 04;13(1):. (PMID: 36671489)
Eur J Cancer. 2004 Apr;40(6):852-7. (PMID: 15120041)
Genes Dis. 2018 Dec 31;6(1):16-24. (PMID: 30906828)
Oncogenesis. 2015 Jul 27;4:e161. (PMID: 26214578)
J Cell Biol. 2012 Feb 20;196(4):395-406. (PMID: 22351925)
Cancer Res. 2023 Jul 5;83(13):2123-2141. (PMID: 37129912)
Dis Model Mech. 2008 Sep-Oct;1(2-3):78-82. (PMID: 19048064)
Mol Cell Biol. 2002 Feb;22(4):1172-83. (PMID: 11809808)
J Clin Endocrinol Metab. 2009 Jan;94(1):204-12. (PMID: 18854392)
Am J Pathol. 2012 Sep;181(3):1017-33. (PMID: 22800756)
N Engl J Med. 2012 Jun 7;366(23):2189-97. (PMID: 22551107)
معلومات مُعتمدة: R01 DK062027 United States DK NIDDK NIH HHS; T32 CA009676 United States CA NCI NIH HHS; T32 CA009676 United States NH NIH HHS; R01 DK062027 United States NH NIH HHS
فهرسة مساهمة: Keywords: COL11A1; Wnt; Wnt/β-catenin; adrenal; adrenocortical carcinoma; collagen; extracellular matrix; targeted therapy; xenograft; β-catenin
تواريخ الأحداث: Date Created: 20230729 Latest Revision: 20240716
رمز التحديث: 20240716
مُعرف محوري في PubMed: PMC10377252
DOI: 10.3390/cancers15143559
PMID: 37509222
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers15143559