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 journalArticle

39 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1650-1663
Number of pages14
JournalCell Reports
Volume5
Issue number6
DOIs
StatePublished - Dec 26 2013

Fingerprint

Catenins
Transcription
Tumors
Neoplasms
Genes
Nocodazole
Colorectal Neoplasms
Phosphotransferases
Down-Regulation
Chemical activation
Growth
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Li, Jiong ; Chen, Xiaohong ; Ding, Xiangming ; Cheng, Yingduan ; Zhao, Bin ; Lai, Zhi-chun ; AlHezaimi, Khalid ; Hakem, Razqallah ; Guan, Kun Liang ; Wang, Cun Yu. / LATS2 suppresses oncogenic Wnt signaling by disrupting β-Catenin/BCL9 interaction. In: Cell Reports. 2013 ; Vol. 5, No. 6. pp. 1650-1663.
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Li, J, Chen, X, Ding, X, Cheng, Y, Zhao, B, Lai, Z, AlHezaimi, K, Hakem, R, Guan, KL & Wang, CY 2013, 'LATS2 suppresses oncogenic Wnt signaling by disrupting β-Catenin/BCL9 interaction', Cell Reports, vol. 5, no. 6, pp. 1650-1663. https://doi.org/10.1016/j.celrep.2013.11.037

LATS2 suppresses oncogenic Wnt signaling by disrupting β-Catenin/BCL9 interaction. / Li, Jiong; Chen, Xiaohong; Ding, Xiangming; Cheng, Yingduan; Zhao, Bin; Lai, Zhi-chun; AlHezaimi, Khalid; Hakem, Razqallah; Guan, Kun Liang; Wang, Cun Yu.

In: Cell Reports, Vol. 5, No. 6, 26.12.2013, p. 1650-1663.

Research output: Contribution to journalArticle

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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

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