title: SnoN Antagonizes the Hippo Kinase Complex to Promote TAZ Signaling during Breast Carcinogenesis.
abstract: SnoN regulates multiple signaling pathways, including TGF-β/Smad and p53, and displays both pro-oncogenic and anti-oncogenic activities in human cancer. We have observed previously that both its intracellular localization and expression levels are sensitive to cell density, suggesting that it may crosstalk with Hippo signaling. Here we report that, indeed, SnoN interacts with multiple components of the Hippo pathway to inhibit the binding of Lats2 to TAZ and the subsequent phosphorylation of TAZ, leading to TAZ stabilization. Consistently, SnoN enhances the transcriptional and oncogenic activities of TAZ, and reducing SnoN decreases TAZ expression as well as malignant progression of breast cancer cells. Interestingly, SnoN itself is downregulated by Lats2 that is activated by the Scribble basolateral polarity protein. Thus, SnoN is a critical component of the Hippo regulatory network that receives signals from the tissue architecture and polarity to coordinate the activity of intracellular signaling pathways.
authors.affiliation: Department of Molecular and Cell Biology, University of California, 16 Barker Hall, MC3204, Berkeley, CA 94720, USA.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Oncomed Pharmaceuticals, Redwood City, CA 94063, USA.
authors.forename: Erwan
authors.initials: E
authors.lastname: Le Scolan
authors.affiliation: ORIC Pharmaceuticals, South San Francisco, CA 94080, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jahchan
authors.affiliation: Departments of Cancer Biology, Cell & Developmental Biology, and Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 190104-6160, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Molecular and Cell Biology, University of California, 16 Barker Hall, MC3204, Berkeley, CA 94720, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cell Biology, University of California, 16 Barker Hall, MC3204, Berkeley, CA 94720, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: kluo@berkeley.edu.
authors.forename: Kunxin
authors.initials: K
authors.lastname: Luo
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C480591:SCRIB protein, human; C060615:SKIL protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: EMT; Hippo; Scribble; SnoN; TAZ; breast cancer; cell polarity