Non-secreting pituitary tumours characterised by enhanced expression of YAP/TAZ.

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  • Additional Information
    • Source:
      Publisher: BioScientifica Country of Publication: England NLM ID: 9436481 Publication Model: Print Cited Medium: Internet ISSN: 1479-6821 (Electronic) Linking ISSN: 13510088 NLM ISO Abbreviation: Endocr Relat Cancer Subsets: MEDLINE
    • Publication Information:
      Publication: Jan. 2011- : Bristol, UK : BioScientifica
      Original Publication: Woodlands, Almondsbury, Bristol, UK : Published for the Society of Endocrinology by the Journal of Endocrinology Ltd., 1994-
    • Subject Terms:
      Adaptor Proteins, Signal Transducing/*metabolism ; Apoptosis Regulatory Proteins/*metabolism ; Intracellular Signaling Peptides and Proteins/*metabolism ; Pituitary Gland/*metabolism ; Pituitary Neoplasms/*metabolism ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism; Aged ; Aged, 80 and over ; Animals ; Cell Line, Tumor ; Female ; Humans ; Male ; Pituitary Neoplasms/genetics ; Protein Serine-Threonine Kinases/genetics ; RNA Interference ; Rats ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins
    • Abstract:
      Tumours of the anterior pituitary can manifest from all endocrine cell types but the mechanisms for determining their specification are not known. The Hippo kinase cascade is a crucial signalling pathway regulating growth and cell fate in numerous organs. There is mounting evidence implicating this in tumour formation, where it is emerging as an anti-cancer target. We previously demonstrated activity of the Hippo kinase cascade in the mouse pituitary and nuclear association of its effectors YAP/TAZ with SOX2-expressing pituitary stem cells. Here, we sought to investigate whether these components are expressed in the human pituitary and if they are deregulated in human pituitary tumours. Analysis of pathway components by immunofluorescence reveals pathway activity during normal human pituitary development and in the adult gland. Poorly differentiated pituitary tumours (null-cell adenomas, adamantinomatous craniopharyngiomas (ACPs) and papillary craniopharyngiomas (PCPs)), displayed enhanced expression of pathway effectors YAP/TAZ. In contrast, differentiated adenomas displayed lower or absent levels. Knockdown of the kinase-encoding Lats1 in GH3 rat mammosomatotropinoma cells suppressed Prl and Gh promoter activity following an increase in YAP/TAZ levels. In conclusion, we have demonstrated activity of the Hippo kinase cascade in the human pituitary and association of high YAP/TAZ with repression of the differentiated state both in vitro and in vivo. Characterisation of this pathway in pituitary tumours is of potential prognostic value, opening up putative avenues for treatments.
    • References:
      Development. 2017 Jun 15;144(12):2141-2152. (PMID: 28506993)
      Nat Genet. 1999 Feb;21(2):182-6. (PMID: 9988269)
      JAMA. 2017 Feb 7;317(5):516-524. (PMID: 28170483)
      Genes Dev. 2010 May;24(9):862-74. (PMID: 20439427)
      Nat Rev Endocrinol. 2014 Jul;10(7):423-35. (PMID: 24821329)
      Brain Tumor Pathol. 2018 Apr;35(2):57-61. (PMID: 29318396)
      Nat Genet. 2014 Feb;46(2):161-5. (PMID: 24413733)
      Cancer Cell. 2016 Jun 13;29(6):783-803. (PMID: 27300434)
      Pituitary. 2014 Dec;17(6):546-56. (PMID: 24356780)
      Ann Endocrinol (Paris). 2015 Jul;76(3):239-47. (PMID: 26072284)
      Mol Neurobiol. 2017 Sep;54(7):4879-4895. (PMID: 27514754)
      Eur J Endocrinol. 2002 Jan;146(1):81-8. (PMID: 11751072)
      Hepatology. 2016 Nov;64(5):1757-1772. (PMID: 27531557)
      Front Physiol. 2016 Mar 31;7:114. (PMID: 27065882)
      Oncotarget. 2015 Feb 28;6(6):4357-68. (PMID: 25738359)
      Cell. 2014 Jul 3;158(1):157-70. (PMID: 24976009)
      Acta Neuropathol. 2014;127(6):927-9. (PMID: 24715106)
      Nat Rev Drug Discov. 2014 Jan;13(1):63-79. (PMID: 24336504)
      Cell. 2012 Dec 21;151(7):1457-73. (PMID: 23245941)
      Endocr Pathol. 2017 Sep;28(3):228-243. (PMID: 28766057)
      Genes Dev. 2007 Nov 1;21(21):2747-61. (PMID: 17974916)
      Sci Rep. 2017 Nov 20;7(1):15856. (PMID: 29158570)
      Acta Neuropathol. 2012 Aug;124(2):259-71. (PMID: 22349813)
      Dev Cell. 2017 Oct 9;43(1):35-47.e4. (PMID: 28943241)
      Cell. 2015 Nov 5;163(4):811-28. (PMID: 26544935)
      EMBO Rep. 2014 Jun;15(6):642-56. (PMID: 24825474)
      Nat Cell Biol. 2011 Aug 01;13(8):877-83. (PMID: 21808241)
      Nat Genet. 2015 Mar;47(3):250-6. (PMID: 25665005)
      Endocrinol Metab Clin North Am. 2017 Jun;46(2):335-374. (PMID: 28476226)
      F1000Prime Rep. 2013 Jun 03;5:17. (PMID: 23755364)
      Dev Cell. 2010 Apr 20;18(4):579-91. (PMID: 20412773)
      Acta Neuropathol. 2017 Oct;134(4):521-535. (PMID: 28821944)
      Dev Cell. 2013 Mar 11;24(5):459-71. (PMID: 23484853)
      Nat Commun. 2016 Jun 30;7:11961. (PMID: 27358050)
      Am J Pathol. 2002 Dec;161(6):1997-2001. (PMID: 12466115)
      J Biochem. 2017 Mar 1;161(3):237-244. (PMID: 28003431)
    • Grant Information:
      G0701018 United Kingdom MRC_ Medical Research Council; MR/L016729/1 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MR/N004272/1 United Kingdom MRC_ Medical Research Council; G1100578 United Kingdom MRC_ Medical Research Council
    • Contributed Indexing:
      Keywords: Hippo signalling; TAZ; YAP; pituitary tumour
    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      0 (Apoptosis Regulatory Proteins)
      0 (Intracellular Signaling Peptides and Proteins)
      0 (Trans-Activators)
      0 (Transcription Factors)
      0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
      0 (WWTR1 protein, human)
      0 (WWTR1 protein, rat)
      0 (YAP-Signaling Proteins)
      0 (YAP1 protein, human)
      0 (Yap1 protein, rat)
      EC 2.7.11.1 (Lats1 protein, rat)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
    • Publication Date:
      Date Created: 20180825 Date Completed: 20200303 Latest Revision: 20220129
    • Publication Date:
      20250114
    • Accession Number:
      PMC6215911
    • Accession Number:
      10.1530/ERC-18-0330
    • Accession Number:
      30139767