SnoN Antagonizes the Hippo Kinase Complex to Promote TAZ Signaling during Breast Carcinogenesis.
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.
['Zhu|Qingwei|Q|', 'Le Scolan|Erwan|E|', 'Jahchan|Nadine|N|', 'Ji|Xiaodan|X|', 'Xu|Albert|A|', 'Luo|Kunxin|K|']
D000217:Acyltransferases D000818:Animals D001943:Breast Neoplasms D063646:Carcinogenesis D002452:Cell Count D002460:Cell Line D045744:Cell Line, Tumor D016764:Cell Polarity D004847:Epithelial Cells D005260:Female D000090683:Hippo Signaling Pathway D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008565:Membrane Proteins D008807:Mice, Inbred BALB C D010766:Phosphorylation D011485:Protein Binding D017346:Protein Serine-Threonine Kinases D055550:Protein Stability D011518:Proto-Oncogene Proteins D015398:Signal Transduction D014157:Transcription Factors D014158:Transcription, Genetic D025521:Tumor Suppressor Proteins
SnoN Hippo TAZ breast cancer Scribble EMT cell polarity