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A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.

التفاصيل البيبلوغرافية
العنوان: A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.
المؤلفون: Mello SS; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Valente LJ; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Raj N; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Seoane JA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Flowers BM; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., McClendon J; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Bieging-Rolett KT; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Lee J; Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA., Ivanochko D; Princess Margaret Cancer Centre, Structural Genomics Consortium and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada., Kozak MM; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA., Chang DT; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Longacre TA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA., Koong AC; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Arrowsmith CH; Princess Margaret Cancer Centre, Structural Genomics Consortium and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada., Kim SK; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA., Vogel H; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA., Wood LD; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Hruban RH; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Curtis C; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA., Attardi LD; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: attardi@stanford.edu.
المصدر: Cancer cell [Cancer Cell] 2017 Oct 09; Vol. 32 (4), pp. 460-473.e6.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press, c2002-
مواضيع طبية MeSH: Nuclear Proteins/*physiology , Pancreatic Neoplasms/*genetics , Protein Tyrosine Phosphatases, Non-Receptor/*physiology , Transcription Factors/*physiology , Tumor Suppressor Protein p53/*physiology, Animals ; Cell Cycle Proteins ; Cell Proliferation ; Cell Transformation, Neoplastic ; Gene Expression Profiling ; Humans ; Mice ; Mutation ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/prevention & control ; Signal Transduction
مستخلص: The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p53 53,54 TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and is necessary and sufficient for pancreatic cancer suppression, like p53. We show that p53 deficiency promotes Yap signaling and that PTPN14 and TP53 mutations are mutually exclusive in human cancers. These studies uncover a p53-Ptpn14-Yap pathway that is integral to p53-mediated tumor suppression.
(Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)
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Comment in: Nat Rev Cancer. 2017 Dec;17 (12 ):706-707. (PMID: 29123244)
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معلومات مُعتمدة: R01 CA140875 United States CA NCI NIH HHS; R21 CA169673 United States CA NCI NIH HHS; R35 CA197591 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Hippo pathway; Ptpn14; YAP; mouse model; p53; pancreas cancer; transactivation domain; tumor suppressor
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (Nuclear Proteins)
0 (TP53 protein, human)
0 (Transcription Factors)
0 (Tumor Suppressor Protein p53)
0 (YY1AP1 protein, human)
EC 3.1.3.48 (PTPN14 protein, human)
EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
تواريخ الأحداث: Date Created: 20171011 Date Completed: 20171031 Latest Revision: 20220331
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5659188
DOI: 10.1016/j.ccell.2017.09.007
PMID: 29017057
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-3686
DOI:10.1016/j.ccell.2017.09.007