دورية أكاديمية
أعرض في EDS

KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway.

التفاصيل البيبلوغرافية
العنوان: KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway.
المؤلفون: Fujii T; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Nakano Y; Department of Pediatrics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan., Hagita D; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Onishi N; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Endo A; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Nakagawa M; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Yoshiura T; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Otsuka Y; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Takeuchi S; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Suzuki M; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Shimizu Y; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Toyooka T; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Matsushita Y; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Hibiya Y; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Tomura S; Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Kondo A; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Wada K; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan., Ichimura K; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan., Tomiyama A; Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.; Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan.; Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
المصدر: Cancers [Cancers (Basel)] 2023 Dec 19; Vol. 16 (1). Date of Electronic Publication: 2023 Dec 19.
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: Here, we investigated the detailed molecular oncogenic mechanisms of a novel receptor tyrosine kinase (RTK) fusion, KLC1-ROS1 , with an adapter molecule, KLC1, and an RTK, ROS1, discovered in pediatric glioma, and we explored a novel therapeutic target for glioma that possesses oncogenic RTK fusion. When wild-type ROS1 and KLC1-ROS1 fusions were stably expressed in the human glioma cell lines A172 and U343MG, immunoblotting revealed that KLC1-ROS1 fusion specifically activated the JAK2-STAT3 pathway, a major RTK downstream signaling pathway, when compared with wild-type ROS1 . Immunoprecipitation of the fractionated cell lysates revealed a more abundant association of the KLC1-ROS1 fusion with JAK2 than that observed for wild-type ROS1 in the cytosolic fraction. A mutagenesis study of the KLC1-ROS1 fusion protein demonstrated the fundamental roles of both the KLC1 and ROS1 domains in the constitutive activation of KLC1-ROS1 fusion. Additionally, in vitro assays demonstrated that KLC1-ROS1 fusion upregulated cell proliferation, invasion, and chemoresistance when compared to wild-type ROS1. Combination treatment with the chemotherapeutic agent temozolomide and an inhibitor of ROS1, JAK2, or a downstream target of STAT3, demonstrated antitumor effects against KLC1-ROS1 fusion-expressing glioma cells. Our results demonstrate that KLC1-ROS1 fusion exerts oncogenic activity through serum-independent constitutive activation, resulting in specific activation of the JAK-STAT pathway. Our data suggested that molecules other than RTKs may serve as novel therapeutic targets for RTK fusion in gliomas.
References: Molecules. 2023 Jun 09;28(12):. (PMID: 37375228)
Biochim Biophys Acta. 2009 Jan;1795(1):37-52. (PMID: 18778756)
Signal Transduct Target Ther. 2020 Mar 12;5(1):28. (PMID: 32296047)
Science. 2020 Jun 5;368(6495):1132-1135. (PMID: 32499443)
Cancers (Basel). 2020 Oct 01;12(10):. (PMID: 33019722)
Cancers (Basel). 2017 Sep 05;9(9):. (PMID: 28872581)
Mod Pathol. 2021 Apr;34(4):735-747. (PMID: 32968185)
Oncogene. 2016 Jul 21;35(29):3854-3865. (PMID: 26657151)
Front Neurol. 2021 Oct 04;12:715206. (PMID: 34671307)
Mol Oncol. 2009 Aug;3(4):297-307. (PMID: 19615955)
Neuro Oncol. 2023 Oct 4;25(Supplement_4):iv1-iv99. (PMID: 37793125)
Cytokine Growth Factor Rev. 2019 Oct;49:23-31. (PMID: 31711797)
Mol Cell Biol. 1986 Aug;6(8):3000-4. (PMID: 3023956)
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):916-21. (PMID: 12538861)
PLoS One. 2012;7(2):e31323. (PMID: 22347464)
Cold Spring Harb Perspect Biol. 2013 May 01;5(5):a017459. (PMID: 23637288)
PLoS One. 2021 Jan 29;16(1):e0237554. (PMID: 33513156)
Cells. 2019 Aug 08;8(8):. (PMID: 31398915)
Clin Cancer Res. 2013 Aug 1;19(15):4040-5. (PMID: 23719267)
Semin Cancer Biol. 2015 Dec;35 Suppl:S25-S54. (PMID: 25892662)
Oncogene Res. 1987 Jul;1(2):169-78. (PMID: 3329713)
Cancer Genomics Proteomics. 2021 May-Jun;18(3):167-196. (PMID: 33893073)
Curr Oncol Rep. 2021 Jun 14;23(8):94. (PMID: 34125313)
Mol Cell Biol. 1986 Sep;6(9):3109-16. (PMID: 3785223)
Ann Pathol. 2023 Nov;43(6):462-474. (PMID: 37635016)
Nat Rev Clin Oncol. 2021 Jan;18(1):35-55. (PMID: 32760015)
Science. 1994 Jun 3;264(5164):1415-21. (PMID: 8197455)
Semin Cancer Biol. 2019 Oct;58:118-129. (PMID: 30685341)
Nat Rev Urol. 2020 Nov;17(11):613-625. (PMID: 33046892)
Brain Tumor Pathol. 2019 Jan;36(1):14-19. (PMID: 30350109)
Oncogene. 2023 Jun;42(24):1959-1969. (PMID: 37149665)
Int J Mol Sci. 2023 Jul 05;24(13):. (PMID: 37446288)
Curr Oncol. 2023 Feb 04;30(2):1893-1902. (PMID: 36826108)
JTO Clin Res Rep. 2020 Apr 28;1(3):100048. (PMID: 34589944)
Cancers (Basel). 2020 Nov 06;12(11):. (PMID: 33172113)
J Biol Chem. 1996 Aug 23;271(34):20494-500. (PMID: 8702790)
EBioMedicine. 2019 Jul;45:92-107. (PMID: 31204277)
Cancers (Basel). 2020 Dec 04;12(12):. (PMID: 33291680)
Proc Natl Acad Sci U S A. 1987 Dec;84(24):9270-4. (PMID: 2827175)
Oncogene. 2021 Jun;40(24):4079-4093. (PMID: 34079087)
Clin Transl Oncol. 2016 Nov;18(11):1062-1071. (PMID: 26960561)
Cancer Res. 2014 Jul 15;74(14):3790-801. (PMID: 24830726)
Cell Death Dis. 2010 Jul 29;1:e60. (PMID: 21364665)
Med Res Rev. 2011 Sep;31(5):794-818. (PMID: 20687158)
Fluids Barriers CNS. 2020 Nov 18;17(1):69. (PMID: 33208141)
Cancer Res. 2019 Feb 1;79(3):546-556. (PMID: 30538120)
Nat Rev Cancer. 2007 Apr;7(4):233-45. (PMID: 17361217)
Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):240-7. (PMID: 26518652)
Mol Ther. 2014 Sep;22(9):1614-24. (PMID: 25034357)
فهرسة مساهمة: Keywords: JAK-STAT pathway; KLC1-ROS1 fusion; glioma; oncogene
تواريخ الأحداث: Date Created: 20240111 Latest Revision: 20240114
رمز التحديث: 20240114
مُعرف محوري في PubMed: PMC10778328
DOI: 10.3390/cancers16010009
PMID: 38201436
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers16010009