LATS2 Suppresses Oncogenic Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction

Jiong Li; Xiaohong Chen; Xiangming Ding; Yingduan Cheng; Bin Zhao; Zhi-chun Lai; Khalid Al Hezaimi; Razqallah Hakem; Kun-liang Guan; Cun-Yu Wang

doi:10.1016/j.celrep.2013.11.037

Cell Reports (Dec 2013)

LATS2 Suppresses Oncogenic Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction

Jiong Li,
Xiaohong Chen,
Xiangming Ding,
Yingduan Cheng,
Bin Zhao,
Zhi-chun Lai,
Khalid Al Hezaimi,
Razqallah Hakem,
Kun-liang Guan,
Cun-Yu Wang

Affiliations

Jiong Li: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Xiaohong Chen: Department of Otolaryngology and Head and Neck Surgery, Affiliated Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing 100730, China
Xiangming Ding: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Yingduan Cheng: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Bin Zhao: Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
Zhi-chun Lai: Departments of Biology and Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
Khalid Al Hezaimi: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Razqallah Hakem: Division of Cellular & Molecular Biology, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, ON M5G 2M9, Canada
Kun-liang Guan: Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
Cun-Yu Wang: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA

DOI: https://doi.org/10.1016/j.celrep.2013.11.037
Journal volume & issue: Vol. 5, no. 6
pp. 1650 – 1663

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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