دورية أكاديمية
أعرض في EDS

Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.

التفاصيل البيبلوغرافية
العنوان: Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.
المؤلفون: Duong VT; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Ha M; Department of Nuclear Medicine and Medical Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Kim J; Department of Convergence Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Kim JY; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Park S; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Reshma KM; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Han ME; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Lee D; Department of Convergence Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Kim YH; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea.; Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Oh SO; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea. hedgehog@pusan.ac.kr.
المصدر: Journal of translational medicine [J Transl Med] 2024 Aug 29; Vol. 22 (1), pp. 800. Date of Electronic Publication: 2024 Aug 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2003-
مواضيع طبية MeSH: Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , Pancreatic Neoplasms*/genetics , Cell Movement* , rab GTP-Binding Proteins*/metabolism , Focal Adhesions*/metabolism , Integrins*/metabolism, Humans ; Cell Line, Tumor ; Focal Adhesion Kinase 1/metabolism ; Female ; Male ; Signal Transduction ; Middle Aged ; Prognosis ; Gene Expression Regulation, Neoplastic ; Endosomes/metabolism ; Disease Progression
مستخلص: Background: Recycling of integrin via endosomal vesicles is critical for the migration of cancer cells, which leads to the metastasis of pancreatic cancer and devastating cancer-related death. So, new diagnostic and therapeutic molecules which target the recycling of endosomal vesicles need to be developed.
Methods: Public databases including TCGA, ICGC, GSE21501, GSE28735, and GENT are analyzed to derive diagnostic and therapeutic targets. To reveal biological roles and underlying mechanisms of molecular targets, various molecular biological experiments were conducted.
Results: First, we identified UNC13D's overexpression in patients with pancreatic cancer (n = 824) and its prognostic significance and high hazard ratio (HR) in four independent pancreatic cancer cohorts (TCGA, n = 178, p = 0.014, HR = 3.629; ICGC, n = 91, p = 0.000, HR = 4.362; GSE21501, n = 102, p = 0.002, HR = 2.339; GSE28735, n = 45, p = 0.022, HR = 2.681). Additionally, its expression is associated with the clinicopathological progression of pancreatic cancer. Further biological studies have shown that UNC13D regulates the migration of pancreatic cancer cells by coupling the exocytosis of recycling endosomes with focal adhesion turnover via the regulation of FAK phosphorylation. Immunoprecipitation and immunocytochemistry showed the formation of the RAB11-UNC13D-FAK axis in endosomes during integrin recycling. We observed that UNC13D directly interacted with the FERM domain of FAK and regulated FAK phosphorylation in a calcium-dependent manner. Finally, we found co-expression of UNC13D and FAK showed the poorest survival (TCGA, p = 0.000; ICGC, p = 0.036; GSE28735, p = 0.006).
Conclusions: We highlight that UNC13D, a novel prognostic factor, promotes pancreatic cancer progression by coupling integrin recycling with focal adhesion turnover via the RAB11-UNC13D-FAK axis for the migration of pancreatic cancer cells.
(© 2024. The Author(s).)
References: Nature. 1994 Dec 22-29;372(6508):786-91. (PMID: 7997267)
Cancer Biol Med. 2021 Feb 15;18(1):206-214. (PMID: 33628595)
J Cell Biol. 2007 Feb 26;176(5):667-80. (PMID: 17325207)
Adv Sci (Weinh). 2021 Aug;8(16):e2100250. (PMID: 34151545)
Traffic. 2018 Dec;19(12):899-909. (PMID: 30054969)
J Cell Biol. 2012 Apr 16;197(2):301-12. (PMID: 22508512)
Adv Drug Deliv Rev. 2011 Jul 18;63(8):610-5. (PMID: 21118706)
Lancet Oncol. 2024 Feb;25(2):167-170. (PMID: 38301687)
J Cell Sci. 2000 Oct;113 ( Pt 20):3673-8. (PMID: 11017882)
Nat Commun. 2022 May 10;13(1):2543. (PMID: 35538070)
Med Oncol. 2015 Jan;32(1):372. (PMID: 25428385)
J Proteomics. 2013 Apr 26;82:35-51. (PMID: 23416715)
Front Immunol. 2013 Nov 18;4:359. (PMID: 24302923)
Biochim Biophys Acta. 2016 Sep;1863(9):2189-200. (PMID: 27212270)
Curr Mol Med. 2013 Mar;13(3):340-51. (PMID: 23331006)
Nat Cell Biol. 2005 Jun;7(6):581-90. (PMID: 15895076)
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68. (PMID: 15688067)
Biomed Pharmacother. 2022 Jul;151:113114. (PMID: 35594704)
Nat Cell Biol. 2002 Apr;4(4):E97-100. (PMID: 11944043)
Anticancer Res. 2010 Mar;30(3):867-71. (PMID: 20393008)
Biochem J. 2000 Jul 1;349(Pt 1):247-53. (PMID: 10861235)
Int J Cell Biol. 2012;2012:310616. (PMID: 22319531)
Exp Hematol Oncol. 2023 Sep 25;12(1):83. (PMID: 37749625)
Nat Cell Biol. 2000 May;2(5):249-56. (PMID: 10806474)
Cancer Res. 2021 Feb 15;81(4):986-1000. (PMID: 33310726)
Cancer Res. 2017 Jun 1;77(11):2990-3000. (PMID: 28416483)
J Immunol. 2008 May 15;180(10):6786-97. (PMID: 18453599)
J Cell Biol. 2005 May 9;169(3):515-26. (PMID: 15866889)
Biochim Biophys Acta Mol Cell Res. 2021 Sep;1868(10):119096. (PMID: 34242681)
Nat Rev Cancer. 2018 Sep;18(9):533-548. (PMID: 30002479)
Biomark Res. 2024 Jan 25;12(1):13. (PMID: 38273343)
Cell. 2007 Jun 15;129(6):1177-87. (PMID: 17574028)
Mol Cell Biol. 2006 Jul;26(13):5155-67. (PMID: 16782899)
Nat Cell Biol. 2004 Feb;6(2):154-61. (PMID: 14743221)
Oncotarget. 2016 Jul 5;7(27):42553-42565. (PMID: 27283771)
Cancer Res. 2019 Jun 1;79(11):2878-2891. (PMID: 30975647)
Nat Cell Biol. 2016 May;18(5):491-503. (PMID: 27043085)
Nat Cell Biol. 2015 Nov;17(11):1412-21. (PMID: 26436690)
Immunol Rev. 2016 Sep;273(1):249-65. (PMID: 27558339)
Trends Cancer. 2023 Apr;9(4):293-308. (PMID: 36804341)
Mol Cell. 2008 Jan 18;29(1):9-22. (PMID: 18206965)
Trends Cell Biol. 2010 Feb;20(2):71-8. (PMID: 20061150)
Biochem Soc Trans. 2020 Feb 28;48(1):83-93. (PMID: 32065228)
Nat Rev Mol Cell Biol. 2010 Nov;11(11):802-14. (PMID: 20966971)
J Cell Biol. 2018 Aug 6;217(8):2877-2890. (PMID: 29930202)
Nat Immunol. 2007 Mar;8(3):257-67. (PMID: 17237785)
Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):333-348. (PMID: 29717230)
Traffic. 2012 Apr;13(4):610-25. (PMID: 22222055)
Cell Death Dis. 2022 Oct 25;13(10):896. (PMID: 36280663)
CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
Elife. 2019 Sep 03;8:. (PMID: 31478830)
J Biol Chem. 2016 Feb 12;291(7):3423-38. (PMID: 26637356)
Int J Biol Sci. 2023 May 15;19(9):2711-2724. (PMID: 37324948)
Br J Cancer. 2010 Feb 16;102(4):710-8. (PMID: 20087351)
Nat Commun. 2020 May 15;11(1):2416. (PMID: 32415208)
Oncotarget. 2017 May 30;8(22):36033-36039. (PMID: 28415599)
Oncogene. 2011 Jan 13;30(2):153-66. (PMID: 20802513)
معلومات مُعتمدة: NRF-2022R1A5A2027161 Medical Research Center (MRC) Program; NRF-2022R1A2C1003930 Mid-career Research Grant
فهرسة مساهمة: Keywords: FAK; Focal adhesion; Integrin; Migration; Pancreatic cancer; Prognosis; RAB11; UNC13D
المشرفين على المادة: EC 3.6.5.2 (rab GTP-Binding Proteins)
0 (Integrins)
EC 3.6.1.- (rab11 protein)
EC 2.7.10.2 (Focal Adhesion Kinase 1)
EC 2.7.10.2 (PTK2 protein, human)
تواريخ الأحداث: Date Created: 20240829 Date Completed: 20240830 Latest Revision: 20240902
رمز التحديث: 20240902
مُعرف محوري في PubMed: PMC11360766
DOI: 10.1186/s12967-024-05630-9
PMID: 39210440
قاعدة البيانات: MEDLINE
الوصف
تدمد:1479-5876
DOI:10.1186/s12967-024-05630-9