دورية أكاديمية
أعرض في EDS

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

التفاصيل البيبلوغرافية
العنوان: CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.
المؤلفون: Yang J; TVHS Department of Veterans Affairs, Nashville, TN, 37212, USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA., Bergdorf K; TVHS Department of Veterans Affairs, Nashville, TN, 37212, USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA., Yan C; TVHS Department of Veterans Affairs, Nashville, TN, 37212, USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA., Luo W; TVHS Department of Veterans Affairs, Nashville, TN, 37212, USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA., Chen SC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37203-1742, USA., Ayers GD; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37203-1742, USA., Liu Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37203-1742, USA., Liu X; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37203-1742, USA., Boothby M; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Weiss VL; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Groves SM; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Oleskie AN; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA., Zhang X; Department of Genomic Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX, 77030, USA., Maeda DY; Syntrix Pharmaceuticals, Auburn, WA, 98001, USA., Zebala JA; Syntrix Pharmaceuticals, Auburn, WA, 98001, USA., Quaranta V; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA.; Department of Biochemistry, Vanderbilt University, TN, 37240, Nashville, USA., Richmond A; TVHS Department of Veterans Affairs, Nashville, TN, 37212, USA. ann.richmond@vanderbilt.edu.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37240, USA. ann.richmond@vanderbilt.edu.
المصدر: Molecular cancer [Mol Cancer] 2023 Jun 03; Vol. 22 (1), pp. 92. Date of Electronic Publication: 2023 Jun 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2002-
مواضيع طبية MeSH: Melanoma*/metabolism , Proto-Oncogene Proteins B-raf*/genetics , Receptors, Interleukin-8B*/genetics , Receptors, Interleukin-8B*/metabolism, Animals ; Mice ; Carcinogenesis/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Tumor Microenvironment
مستخلص: Background: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established.
Methods: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven Braf V600E /Pten -/- /Cxcr2 -/- and NRas Q61R /INK4a -/- /Cxcr2 -/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in Braf V600E /Pten -/- and NRas Q61R /INK4a -/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA).
Results: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log 2 fold-change greater than 2 in these three different melanoma models.
Conclusions: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
التعليقات: Update of: bioRxiv. 2023 Mar 04;:. (PMID: 36865260)
References: Elife. 2017 Jun 03;6:. (PMID: 28577314)
Cell. 2017 Nov 2;171(4):934-949.e16. (PMID: 29033130)
Mol Cancer Ther. 2008 Sep;7(9):2649-61. (PMID: 18790747)
Cancer Lett. 2008 Aug 28;267(2):226-44. (PMID: 18579287)
Cell. 2014 Sep 11;158(6):1254-1269. (PMID: 25215486)
J Cell Sci. 2017 Nov 15;130(22):3809-3817. (PMID: 28982712)
J Biol Chem. 2007 Apr 20;282(16):11658-66. (PMID: 17197447)
Carcinogenesis. 2009 Dec;30(12):2023-30. (PMID: 19917631)
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21521-6. (PMID: 19995984)
Cell Rep. 2013 Apr 25;3(4):1140-52. (PMID: 23583175)
Int J Cancer. 2010 Jan 15;126(2):328-36. (PMID: 19585580)
Rom J Morphol Embryol. 2014;55(2 Suppl):575-8. (PMID: 25178327)
Genesis. 2013 Aug;51(8):587-95. (PMID: 23650205)
Nature. 2022 Oct;610(7930):190-198. (PMID: 36131018)
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6. (PMID: 15282370)
Hum Reprod. 2012 Jul;27(7):2107-16. (PMID: 22563025)
Theranostics. 2017 Apr 7;7(6):1543-1588. (PMID: 28529637)
Cancer Lett. 2018 Apr 28;420:72-79. (PMID: 29410248)
Nat Med. 2019 Dec;25(12):1916-1927. (PMID: 31792460)
Cancer Discov. 2014 Dec;4(12):1418-29. (PMID: 25252692)
Int J Mol Sci. 2018 Sep 20;19(10):. (PMID: 30241344)
J Natl Cancer Inst. 2011 Jul 20;103(14):1112-22. (PMID: 21685357)
Front Mol Neurosci. 2019 May 01;12:111. (PMID: 31118886)
Oncogene. 1991 Jul;6(7):1115-24. (PMID: 1861861)
Int J Mol Sci. 2022 Nov 15;23(22):. (PMID: 36430553)
Cells. 2020 Jan 30;9(2):. (PMID: 32019273)
Genesis. 2007 Sep;45(9):593-605. (PMID: 17868096)
J Cell Sci. 2009 Oct 1;122(Pt 19):3502-10. (PMID: 19723802)
Cancer Res. 2009 Feb 15;69(4):1302-13. (PMID: 19190339)
Stem Cells Dev. 2016 Jul 1;25(13):1006-19. (PMID: 27188501)
JCI Insight. 2019 Apr 4;4(7):. (PMID: 30944253)
Cancers (Basel). 2021 Dec 15;13(24):. (PMID: 34944914)
J Med Chem. 2014 Oct 23;57(20):8378-97. (PMID: 25254640)
Respir Res. 2013 Dec 16;14:137. (PMID: 24341382)
Stem Cell Reports. 2015 Sep 8;5(3):314-22. (PMID: 26321140)
Eur J Med Chem. 2020 Jan 1;185:111853. (PMID: 31732253)
J Cell Physiol. 2018 Sep;233(9):6944-6951. (PMID: 29323720)
J Biol Chem. 2021 Oct;297(4):101217. (PMID: 34555410)
Br J Cancer. 2009 May 19;100(10):1638-46. (PMID: 19401689)
J Immunol. 2000 Nov 1;165(9):5269-77. (PMID: 11046061)
J Biol Chem. 2008 Sep 26;283(39):26538-47. (PMID: 18662984)
Genome Med. 2020 Oct 6;12(1):86. (PMID: 33023656)
Breast Cancer Res Treat. 2012 Oct;135(3):737-47. (PMID: 22923236)
Novartis Found Symp. 2004;256:74-89; discussion 89-91, 106-11, 266-9. (PMID: 15027484)
Cancers (Basel). 2022 Jul 23;14(15):. (PMID: 35892852)
Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204)
Front Pharmacol. 2019 Mar 28;10:307. (PMID: 30984000)
J Biol Chem. 2019 Apr 12;294(15):6007-6016. (PMID: 30782842)
Pharmacol Ther. 2009 Jan;121(1):55-68. (PMID: 19026683)
Exp Cell Res. 2011 Mar 10;317(5):575-89. (PMID: 21223965)
Cell Oncol (Dordr). 2021 Feb;44(1):77-92. (PMID: 32910411)
Cytokine. 2022 May;153:155828. (PMID: 35247648)
Cancer Immunol Res. 2021 Feb;9(2):200-213. (PMID: 33177110)
Cell Rep. 2023 May 30;42(5):112451. (PMID: 37119134)
Nat Genet. 2009 May;41(5):544-52. (PMID: 19282848)
معلومات مُعتمدة: R21 CA116022 United States CA NCI NIH HHS; S10 OD023475 United States OD NIH HHS; IK6 BX005225 United States BX BLRD VA; S10 OD016355 United States OD NIH HHS; T32 CA119925 United States CA NCI NIH HHS; K08 CA240901 United States CA NCI NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; P30 CA021765 United States CA NCI NIH HHS; T32 CA009582 United States CA NCI NIH HHS; I01 BX002301 United States BX BLRD VA; U54 CA217450 United States CA NCI NIH HHS; P30 CA068485 United States CA NCI NIH HHS; T32 CA009592 United States CA NCI NIH HHS; R01 CA116021 United States CA NCI NIH HHS; R01 CA272875 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: CXCR2; Genetic mouse models; Genomic analysis; Melanoma; Tumor immune microenvironment
المشرفين على المادة: EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
0 (Receptors, Interleukin-8B)
0 (Cxcr2 protein, mouse)
تواريخ الأحداث: Date Created: 20230603 Date Completed: 20230608 Latest Revision: 20231006
رمز التحديث: 20231006
مُعرف محوري في PubMed: PMC10239119
DOI: 10.1186/s12943-023-01789-9
PMID: 37270599
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4598
DOI:10.1186/s12943-023-01789-9