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LATS2 suppresses oncogenic Wnt signaling by disrupting β-catenin/BCL9 interaction.

Abstract
Abnormal activation of Wnt/β-catenin-mediated transcription is associated with a variety of human cancers. Here, we report that LATS2 inhibits oncogenic Wnt/β-catenin-mediated transcription by disrupting the β-catenin/BCL9 interaction. LATS2 directly interacts with β-catenin and is present on Wnt target gene promoters. Mechanistically, LATS2 inhibits the interaction between BCL9 and β-catenin and subsequent recruitment of BCL9, independent of LATS2 kinase activity. LATS2 is downregulated and inversely correlated with the levels of Wnt target genes in human colorectal cancers. Moreover, nocodazole, an antimicrotubule drug, potently induces LATS2 to suppress tumor growth in vivo by targeting β-catenin/BCL9. Our results suggest that LATS2 is not only a key tumor suppressor in human cancer but may also be an important target for anticancer therapy.
AuthorsJiong Li, Xiaohong Chen, Xiangming Ding, Yingduan Cheng, Bin Zhao, Zhi-Chun Lai, Khalid Al Hezaimi, Razqallah Hakem, Kun-Liang Guan, Cun-Yu Wang
JournalCell reports (Cell Rep) Vol. 5 Issue 6 Pg. 1650-63 (Dec 26 2013) ISSN: 2211-1247 [Electronic] United States
PMID24360964 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • BCL9 protein, human
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • beta Catenin
  • LATS2 protein, human
  • Protein-Serine-Threonine Kinases
Topics
  • Cell Line, Tumor
  • Colorectal Neoplasms (genetics, metabolism)
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Neoplasm Proteins (metabolism)
  • Protein Binding
  • Protein-Serine-Threonine Kinases (metabolism)
  • Transcription, Genetic
  • Tumor Suppressor Proteins (metabolism)
  • Wnt Signaling Pathway
  • beta Catenin (metabolism)

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