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 AlHezaimi; Razqallah Hakem; Kun Liang Guan; Cun Yu Wang

doi:10.1016/j.celrep.2013.11.037

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 AlHezaimi, Razqallah Hakem, Kun Liang Guan, Cun Yu Wang

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

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 invivo 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.

Original language	English (US)
Pages (from-to)	1650-1663
Number of pages	14
Journal	Cell Reports
Volume	5
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2013.11.037
State	Published - Dec 26 2013

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2013.11.037

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title = "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 invivo 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.",

author = "Jiong Li and Xiaohong Chen and Xiangming Ding and Yingduan Cheng and Bin Zhao and Lai, {Zhi Chun} and Khalid AlHezaimi and Razqallah Hakem and Guan, {Kun Liang} and Wang, {Cun Yu}",

note = "Funding Information: This work was supported by NICDR grants DE015964, DE17684, and DE13848 and NCI grant CA132134 to C.-Y.W. ",

year = "2013",

month = dec,

day = "26",

doi = "10.1016/j.celrep.2013.11.037",

language = "English (US)",

volume = "5",

pages = "1650--1663",

journal = "Cell Reports",

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TY - JOUR

T1 - LATS2 suppresses oncogenic Wnt signaling by disrupting β-Catenin/BCL9 interaction

AU - Li, Jiong

AU - Chen, Xiaohong

AU - Ding, Xiangming

AU - Cheng, Yingduan

AU - Zhao, Bin

AU - Lai, Zhi Chun

AU - AlHezaimi, Khalid

AU - Hakem, Razqallah

AU - Guan, Kun Liang

AU - Wang, Cun Yu

N1 - Funding Information: This work was supported by NICDR grants DE015964, DE17684, and DE13848 and NCI grant CA132134 to C.-Y.W.

PY - 2013/12/26

Y1 - 2013/12/26

N2 - 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 invivo 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.

AB - 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 invivo 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.

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JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

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

Abstract

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