ZDHHC1 downregulates LIPG and inhibits colorectal cancer growth via IGF2BP1 Palmitoylation.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9432230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5500 (Electronic) Linking ISSN: 09291903 NLM ISO Abbreviation: Cancer Gene Ther Subsets: MEDLINE
    • Publication Information:
      Publication: <2002->: London : Nature Publishing Group
      Original Publication: Norwalk, CT : Appleton & Lange, c1994-
    • Subject Terms:
      Acyltransferases*/genetics ; Acyltransferases*/metabolism ; Cell Proliferation* ; Colorectal Neoplasms*/metabolism ; Colorectal Neoplasms*/genetics ; Colorectal Neoplasms*/pathology ; Down-Regulation* ; Lipoylation*; Animals ; Humans ; Male ; Mice ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Lipase/metabolism ; Lipase/genetics ; Mice, Nude
    • Abstract:
      Alteration in lipid metabolism is recognized as a hallmark feature of colorectal cancer (CRC). Protein S-palmitoylation plays a critical role in many different cellular processes including protein-lipid interaction. Zinc Finger DHHC-Type Containing 1 (ZDHHC1, also known as ZNF377) belongs to the palmitoyl-transferase ZDHHC family, and is a potential tumor suppressor. However, our knowledge of the functional roles of ZDHHC1 in CRC is limited. We discovered that ZDHHC1 expression was downregulated in CRC tissues and that low levels of ZDHHC1 were associated with unfavorable prognosis. Functional studies showed that ZDHHC1 inhibited CRC cell proliferation and invasion in vitro and in vivo. We also found that lipase G (LIPG) is negatively regulated by ZDHHC1 and plays a key role in CRC cell growth through lipid storage. Additionally, we demonstrated that ZDHHC1 functions as a IGF2BP1-palmitoylating enzyme that induces S-palmitoylation at IGF2BP1-C337, which results in downregulated LIPG expression via m6A modification. Mechanistic investigations revealed that the ZDHHC1/IGF2BP1/LIPG signaling axis is associated with inhibition of CRC cell growth. Our study uncovers the potential role of ZDHHC1 in CRC, including inhibition of CRC growth by reducing the stability of LIPG mRNA in an m6A dependent-manner by palmitoylation of IGF2BP1.
      (© 2024. The Author(s).)
    • References:
      Int J Biol Sci. 2023 Jan 1;19(2):449-464. (PMID: 36632454)
      Lipids Health Dis. 2019 Jan 26;18(1):29. (PMID: 30684960)
      Biochim Biophys Acta. 2012 Jul;1821(7):1003-11. (PMID: 23075452)
      Chem Biol Interact. 2016 Nov 25;259(Pt B):211-222. (PMID: 27067293)
      Nat Rev Endocrinol. 2014 Aug;10(8):455-465. (PMID: 24935119)
      Metabolites. 2022 Feb 26;12(3):. (PMID: 35323656)
      Mol Oncol. 2023 Jan;17(1):3-26. (PMID: 36018061)
      EMBO Mol Med. 2018 Mar;10(3):. (PMID: 29449326)
      Exp Biol Med (Maywood). 2017 Jun;242(11):1150-1157. (PMID: 28485685)
      Oncol Lett. 2019 May;17(5):4351-4360. (PMID: 30944629)
      Nature. 2012 Apr 29;485(7397):201-6. (PMID: 22575960)
      J Exp Med. 2021 Jan 4;218(1):. (PMID: 33601415)
      Cancer Lett. 2021 Dec 1;522:255-268. (PMID: 34563640)
      Int J Androl. 2010 Feb;33(1):e207-15. (PMID: 19780863)
      J Cell Biochem. 2023 Jan;124(1):3-16. (PMID: 36334309)
      Eur J Surg Oncol. 2022 Jul;48(7):1664-1670. (PMID: 35339340)
      JAMA. 2021 Feb 16;325(7):669-685. (PMID: 33591350)
      Eur J Cell Biol. 2018 Jun;97(5):319-338. (PMID: 29602512)
      Cell. 2018 Apr 5;173(2):371-385.e18. (PMID: 29625053)
      Elife. 2018 Jan 19;7:. (PMID: 29350614)
      Diagn Pathol. 2013 Mar 19;8:45. (PMID: 23510199)
      Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1788-94. (PMID: 23723371)
      Histopathology. 2011 Apr;58(5):766-72. (PMID: 21401706)
      EMBO Rep. 2018 Oct;19(10):. (PMID: 30232163)
      Br J Cancer. 2019 Jun;120(12):1090-1098. (PMID: 31092908)
      Curr Opin Gastroenterol. 2022 Mar 1;38(2):162-167. (PMID: 35098938)
      Physiol Rev. 2015 Apr;95(2):341-76. (PMID: 25834228)
      Nat Chem Biol. 2006 Nov;2(11):584-90. (PMID: 17051234)
      Oncogene. 2021 Sep;40(35):5416-5426. (PMID: 34282274)
      Biochem Soc Trans. 2017 Aug 15;45(4):923-8. (PMID: 28630137)
      Nat Rev Mol Cell Biol. 2007 Jan;8(1):74-84. (PMID: 17183362)
      Cancer Biol Med. 2014 Mar;11(1):1-19. (PMID: 24738035)
      CA Cancer J Clin. 2023 May-Jun;73(3):233-254. (PMID: 36856579)
      CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
      J Lipid Res. 2005 May;46(5):977-87. (PMID: 15722560)
      Theranostics. 2020 Jul 25;10(21):9495-9511. (PMID: 32863941)
      J Lipid Res. 2006 Jun;47(6):1118-27. (PMID: 16582420)
    • Accession Number:
      EC 2.3.- (Acyltransferases)
      EC 3.1.1.3 (Lipase)
      EC 2.3.1.- (ZDHHC1 protein, human)
      0 (IGF2BP1 protein, human)
      EC 3.1.1.3 (LIPG protein, human)
    • Publication Date:
      Date Created: 20240728 Date Completed: 20240916 Latest Revision: 20240924
    • Publication Date:
      20240925
    • Accession Number:
      PMC11405259
    • Accession Number:
      10.1038/s41417-024-00808-1
    • Accession Number:
      39069526