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 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.
authors.affiliation: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Affiliated Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing 100730, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Ding
authors.affiliation: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yingduan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Departments of Biology and Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Lai
authors.affiliation: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eng.A.B Research Chair for Growth Factors and Bone Regeneration, Division of Periodontology, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al Hezaimi
authors.affiliation: Division of Cellular & Molecular Biology, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, ON M5G 2M9, Canada.
authors.forename: Razqallah
authors.initials: R
authors.lastname: Hakem
authors.affiliation: Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.affiliation: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: cunywang@ucla.edu.
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C111180:BCL9 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases