دورية أكاديمية
أعرض في EDS

A feed forward loop enforces YAP/TAZ signaling during tumorigenesis.

التفاصيل البيبلوغرافية
العنوان: A feed forward loop enforces YAP/TAZ signaling during tumorigenesis.
المؤلفون: Gill MK; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Donnelly Centre, University of Toronto, Toronto, ON, M5S 3E1, Canada., Christova T; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Donnelly Centre, University of Toronto, Toronto, ON, M5S 3E1, Canada., Zhang YY; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Gregorieff A; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.; Department of Pathology, McGill University and Research Institute of the McGill University Health Center, Montreal, H4A 3J1, QC, Canada., Zhang L; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, 999077, Hong Kong, China.; City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangdong, 518057, China., Narimatsu M; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Song S; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Donnelly Centre, University of Toronto, Toronto, ON, M5S 3E1, Canada., Xiong S; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Couzens AL; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Tong J; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada., Krieger JR; SPARC BioCentre, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada., Moran MF; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.; SPARC BioCentre, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada., Zlotta AR; Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, M5G 1X5, ON, Canada., van der Kwast TH; Department of Pathology, Toronto General Hospital, University Health Network, Toronto, ON, M5G 2C4, Canada., Gingras AC; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Sicheri F; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Wrana JL; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada., Attisano L; Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada. liliana.attisano@utoronto.ca.; Donnelly Centre, University of Toronto, Toronto, ON, M5S 3E1, Canada. liliana.attisano@utoronto.ca.
المصدر: Nature communications [Nat Commun] 2018 Aug 29; Vol. 9 (1), pp. 3510. Date of Electronic Publication: 2018 Aug 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Adaptor Proteins, Signal Transducing/*metabolism , Carcinogenesis/*metabolism , Phosphoproteins/*metabolism , Transcription Factors/*metabolism, Acyltransferases ; Adaptor Proteins, Signal Transducing/genetics ; Carcinogenesis/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Female ; HEK293 Cells ; Humans ; Immunoblotting ; Immunoprecipitation ; Microscopy, Fluorescence ; Phosphoproteins/genetics ; Phosphorylation ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction/genetics ; Signal Transduction/physiology ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism ; Transcription Factors/genetics ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; YAP-Signaling Proteins
مستخلص: In most solid tumors, the Hippo pathway is inactivated through poorly understood mechanisms that result in the activation of the transcriptional regulators, YAP and TAZ. Here, we identify NUAK2 as a YAP/TAZ activator that directly inhibits LATS-mediated phosphorylation of YAP/TAZ and show that NUAK2 induction by YAP/TAZ and AP-1 is required for robust YAP/TAZ signaling. Pharmacological inhibition or loss of NUAK2 reduces the growth of cultured cancer cells and mammary tumors in mice. Moreover, in human patient samples, we show that NUAK2 expression is elevated in aggressive, high-grade bladder cancer and strongly correlates with a YAP/TAZ gene signature. These findings identify a positive feed forward loop in the Hippo pathway that establishes a key role for NUAK2 in enforcing the tumor-promoting activities of YAP/TAZ. Our results thus introduce a new opportunity for cancer therapeutics by delineating NUAK2 as a potential target for re-engaging the Hippo pathway.
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المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Phosphoproteins)
0 (Transcription Factor AP-1)
0 (Transcription Factors)
0 (Tumor Suppressor Proteins)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)
EC 2.3.- (Acyltransferases)
EC 2.3.1.- (TAFAZZIN protein, human)
EC 2.7.1.- (LATS1 protein, human)
EC 2.7.1.11 (LATS2 protein, human)
EC 2.7.11.1 (NUAK2 protein, human)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20180831 Date Completed: 20181217 Latest Revision: 20211204
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6115388
DOI: 10.1038/s41467-018-05939-2
PMID: 30158528
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-018-05939-2