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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.
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http://dx.doi.org/10.1016/j.celrep.2013.11.037 | DOI Listing |
Aging Cell
September 2025
Department of Cell Systems & Anatomy, University of Texas Health San Antonio, San Antonio, Texas, USA.
The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Biochemistry & Molecular Biotechnology, UMass Chan Medical School, Worcester, MA, 01605.
The LIM domain protein LIMD1 is a critical regulator of the Hippo signaling pathway, acting to sequester the kinases LATS1/2 to adherens junctions (AJs) in response to mechanical strain. Here, we identify the molecular basis for LIMD1 binding and recruitment of LATS1/2 to AJs. We show that while the LIM domains of LIMD1 are sufficient for AJ localization and binding to LATS1/2, recruitment of LATS1 to AJ requires both the intrinsically disordered region (IDR) in the N-terminus as well as the LIM domains.
View Article and Find Full Text PDFWorld J Surg Oncol
August 2025
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Orthod Craniofac Res
August 2025
School of Dentistry, University of California Los Angeles, Los Angeles, California, USA.
Objective(s): Yes-Associated Protein (YAP) is a critical regulator of cell proliferation and differentiation, having the capacity to convert differentiated cells into somatic stem cells in several contexts. Here we investigate the plasticity of adult mouse dental epithelial cells by testing the effects of ectopic YAP activation in dental epithelial progenitors and differentiated ameloblasts during incisor renewal.
Materials And Methods: Using mice with dental epithelial deletion of Lats1 and Lats2, which encode negative regulators of YAP, we assessed how ectopic YAP activation altered tissue structure, cell proliferation, and differentiation via histological analysis, EdU/BrdU labeling, and immunostaining.
Front Pharmacol
August 2025
Department of Cardiology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China.
Background: Shenyuan Yiqi Huoxue Capsule (SYYQ) has clinical evidence to improve coronary microvascular dysfunction (CMD) by tonifying qi and removing blood stasis, but the underlying mechanism remains unclear.
Objective: This study aims to explore the mechanism by which SYYQ alleviates CMD through a combination of network analysis and both and experiments.
Methods: First, network pharmacology was employed to predict the mechanism of SYYQ on CMD.