Home LiteratureArticle Details
PMID: 20354134 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis.

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 16 ·No. 8 ·2010-04-15 ·Pages 2229-34

Scott KL, Chin L

Abstract

Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention.

MeSH Terms
Carcinogens/metabolism Cell Transformation, Neoplastic Golgi Apparatus/metabolism Humans Membrane Proteins/physiology Neoplasms/pathology Oncogene Proteins/physiology Signal Transduction
Chemicals
Carcinogens GOLPH3 protein, human Membrane Proteins Oncogene Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Scott Kenneth L
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Chin Lynda
References (50)
50 references, click to expand
  1. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer.
    Nature. 2009 Jun 25;459(7250):1085-90 PMID: 19553991
  2. Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.
    Science. 2004 Oct 1;306(5693):120-4 PMID: 15459394
  3. RCP is a human breast cancer-promoting gene with Ras-activating function.
    J Clin Invest. 2009 Aug;119(8):2171-83 PMID: 19620787
  4. The oligosaccharide moieties of the epidermal growth factor receptor in A-431 cells. Presence of complex-type N-linked chains that contain terminal N-acetylgalactosamine residues.
    J Biol Chem. 1985 Oct 5;260(22):11944-52 PMID: 2995354
  5. Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein.
    J Biol Chem. 2002 Apr 5;277(14):12190-9 PMID: 11786538
  6. Proteomics characterization of abundant Golgi membrane proteins.
    J Biol Chem. 2001 Feb 16;276(7):5152-65 PMID: 11042173
  7. PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking.
    J Cell Biol. 2009 Dec 28;187(7):967-75 PMID: 20026658
  8. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.
    Dev Cell. 2008 Jan;14(1):140-7 PMID: 18160347
  9. Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi.
    Cell. 2003 Aug 8;114(3):299-310 PMID: 12914695
  10. HIP1: trafficking roles and regulation of tumorigenesis.
    Trends Mol Med. 2004 Apr;10(4):194-9 PMID: 15059611
  11. Endocytosis and signalling: intertwining molecular networks.
    Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22 PMID: 19696798
  12. GMx33: a novel family of trans-Golgi proteins identified by proteomics.
    Traffic. 2000 Dec;1(12):963-75 PMID: 11208086
  13. Wingless secretion promotes and requires retromer-dependent cycling of Wntless.
    Nat Cell Biol. 2008 Feb;10(2):178-85 PMID: 18193032
  14. Probing the membrane environment of the TOR kinases reveals functional interactions between TORC1, actin, and membrane trafficking in Saccharomyces cerevisiae.
    Mol Biol Cell. 2007 Aug;18(8):2779-94 PMID: 17507646
  15. C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless.
    Dev Cell. 2008 Jan;14(1):132-9 PMID: 18160346
  16. Retromer.
    Curr Opin Cell Biol. 2008 Aug;20(4):427-36 PMID: 18472259
  17. Subcellular locations of phosphatidylinositol 4-kinase isoforms.
    J Biol Chem. 1997 May 16;272(20):13236-41 PMID: 9148941
  18. Wnt/beta-catenin signaling in development and disease.
    Cell. 2006 Nov 3;127(3):469-80 PMID: 17081971
  19. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network.
    Dev Cell. 2008 Jan;14(1):120-31 PMID: 18160348
  20. Glycosylation of the epidermal growth factor receptor in A-431 cells. The contribution of carbohydrate to receptor function.
    J Biol Chem. 1984 Oct 25;259(20):12586-94 PMID: 6092339
  21. Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae.
    Mol Biol Cell. 2002 Jul;13(7):2486-501 PMID: 12134085
  22. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains.
    J Biol Chem. 2004 Apr 2;279(14):14294-306 PMID: 14732715
  23. Altered receptor trafficking in Huntingtin Interacting Protein 1-transformed cells.
    Cancer Cell. 2003 May;3(5):471-82 PMID: 12781365
  24. A DNA integrity network in the yeast Saccharomyces cerevisiae.
    Cell. 2006 Mar 10;124(5):1069-81 PMID: 16487579
  25. Glycosylation in cellular mechanisms of health and disease.
    Cell. 2006 Sep 8;126(5):855-67 PMID: 16959566
  26. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex.
    Nat Cell Biol. 2008 Feb;10(2):170-7 PMID: 18193037
  27. Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments.
    J Cell Biol. 2008 Oct 6;183(1):143-55 PMID: 18838556
  28. GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.
    Cell. 2009 Oct 16;139(2):337-51 PMID: 19837035
  29. Glycosylation of the epidermal growth factor receptor and its relationship to membrane transport and ligand binding.
    J Biochem. 1988 Sep;104(3):388-96 PMID: 3149275
  30. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers.
    Nat Med. 2004 Nov;10(11):1251-6 PMID: 15502842
  31. Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival.
    J Clin Invest. 2002 Aug;110(3):351-60 PMID: 12163454
  32. Global mapping of the yeast genetic interaction network.
    Science. 2004 Feb 6;303(5659):808-13 PMID: 14764870
  33. Golgi localization of glycosyltransferases requires a Vps74p oligomer.
    Dev Cell. 2008 Apr;14(4):523-34 PMID: 18410729
  34. Enhanced degradation of EGF receptors by a sorting nexin, SNX1.
    Science. 1996 May 17;272(5264):1008-10 PMID: 8638121
  35. Derailed endocytosis: an emerging feature of cancer.
    Nat Rev Cancer. 2008 Nov;8(11):835-50 PMID: 18948996
  36. The RCP-Rab11 complex regulates endocytic protein sorting.
    Mol Biol Cell. 2004 Aug;15(8):3530-41 PMID: 15181150
  37. mTOR and cancer: insights into a complex relationship.
    Nat Rev Cancer. 2006 Sep;6(9):729-34 PMID: 16915295
  38. Aberrant Huntingtin interacting protein 1 in lymphoid malignancies.
    Cancer Res. 2007 Sep 15;67(18):8923-31 PMID: 17875735
  39. Rab GTPases as coordinators of vesicle traffic.
    Nat Rev Mol Cell Biol. 2009 Aug;10(8):513-25 PMID: 19603039
  40. Identification and characterization of a family of Rab11-interacting proteins.
    J Biol Chem. 2001 Oct 19;276(42):39067-75 PMID: 11495908
  41. Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation.
    J Cell Sci. 2007 Dec 15;120(Pt 24):4367-76 PMID: 18057029
  42. The emerging role of the RAB25 small GTPase in cancer.
    Traffic. 2009 Nov;10(11):1561-8 PMID: 19719478
  43. Signal-mediated dynamic retention of glycosyltransferases in the Golgi.
    Science. 2008 Jul 18;321(5887):404-7 PMID: 18635803
  44. Cloning and characterization of a human phosphatidylinositol 4-kinase.
    J Biol Chem. 1994 Nov 18;269(46):28878-84 PMID: 7961848
  45. Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex.
    Nat Cell Biol. 2005 Sep;7(9):880-6 PMID: 16100512
  46. Recycle your receptors with retromer.
    Trends Cell Biol. 2005 Feb;15(2):68-75 PMID: 15695093
  47. GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi.
    Mol Biol Cell. 2006 Jan;17(1):511-24 PMID: 16236792
  48. The multiple roles of PtdIns(4)P -- not just the precursor of PtdIns(4,5)P2.
    J Cell Sci. 2008 Jun 15;121(Pt 12):1955-63 PMID: 18525025
  49. TOR signaling in growth and metabolism.
    Cell. 2006 Feb 10;124(3):471-84 PMID: 16469695
  50. Role of N-glycans in growth factor signaling.
    Glycoconj J. 2004;20(3):207-12 PMID: 15090734
Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-09-1695
Published
2010-04-15
Epub
2010-00-30
Pages
2229-34
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC2855764
Subset
IM
Grants
NIAMS NIH HHS · 5-T32-AR07098-31 · United States
NIAMS NIH HHS · T32 AR007098 · United States
NCI NIH HHS · P50 CA093683 · United States
NCI NIH HHS · R01 CA093947-09 · United States
NCI NIH HHS · R01 CA093947 · United States
NCI NIH HHS · P50 CA93683 · United States
NCI NIH HHS · R01 CA93947 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-09-1695 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2