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

被引：69

作者：

Li, Jiong ^{[1
]}

Chen, Xiaohong ^{[2
]}

Ding, Xiangming ^{[1
]}

Cheng, Yingduan ^{[1
]}

Zhao, Bin ^{[3
]}

Lai, Zhi-chun ^{[4
,5
]}

Al Hezaimi, Khalid ^{[1
,6
]}

Hakem, Razqallah ^{[7
]}

Guan, Kun-liang ^{[3
]}

Wang, Cun-Yu ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Mol Signalling Lab, Div Oral Biol & Med, Los Angeles, CA 90095 USA

[2] Capital Univ Med Sci, Affiliated Beijing Tongren Hosp, Dept Otolaryngol & Head & Neck Surg, Beijing 100730, Peoples R China

[3] Univ Calif San Diego, Dept Pharmacol, Moores Canc Ctr, San Diego, CA 92093 USA

[4] Penn State Univ, Dept Biol, University Pk, PA 16802 USA

[5] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

[6] King Saud Univ, Coll Dent, Div Periodontol, Eng AB Res Chair Growth Factors & Bone Regenerat, Riyadh 11545, Saudi Arabia

[7] Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Dept Cellular & Mol Biol, Toronto, ON M5G 2M9, Canada

来源：

CELL REPORTS | 2013年 / 5卷 / 06期

关键词：

CATENIN-TCF COMPLEX; TUMOR-SUPPRESSOR; BETA-CATENIN; CELL-PROLIFERATION; PROMOTES APOPTOSIS; PROTEIN-KINASE; COLON-CANCER; SIZE-CONTROL; DROSOPHILA; HIPPO;

D O I：

10.1016/j.celrep.2013.11.037

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Abnormal activation of Wnt/beta-catenin-mediated transcription is associated with a variety of human cancers. Here, we report that LATS2 inhibits oncogenic Wnt/beta-catenin-mediated transcription by disrupting the beta-catenin/BCL9 interaction. LATS2 directly interacts with beta-catenin and is present on Wnt target gene promoters. Mechanistically, LATS2 inhibits the interaction between BCL9 and beta-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 beta-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.

引用

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页码：1650 / 1663

页数：14

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