LATS1 (Large Tumor Suppressor 1)
2015-07-01 Helena J Janse van Rensburg  , Xiaolong Yang  , Stacy Visser-Grieve   AffiliationIdentity
Abstract
LATS1 tumor suppressor is a serine\/threonine kinase of the AGC kinase family and a core component of the Hippo pathway in mammals. LATS1 regulates various biological processes such as cell cycle progression, genetic stability, cell motility and adhesion, apoptosis, stem cell renewal and differentiation (Visser and Yang, 2010; Mo et al., 2014). LATS1 performs these functions by phosphorylating various substrates such as transcriptional co-activators YAP and TAZ (Zhao et al., 2007; Hao et al., 2008). LATS1 is also required for tissue homeostasis in both flies and mice (Visser et al., 2010). In addition to its roles in a broad spectrum of normal biological processes, loss of LATS1 has been shown to be important for the development of cancer and resistance to chemotherapeutic drugs (Visser et al., 2010). Therefore, understanding the molecular mechanisms underlying loss-of-LATS1-induced tumorigenesis and drug resistance will shed light on the design of new cancer treatment strategies in the future.
DNA/RNA
Description
Transcription
Proteins

Description
Expression
Localisation
Function
HIPPO Signaling Pathway LATS1 is a key player in the conserved Hippo signaling pathway. Core components of this pathway include the adaptor proteins Sav1 and MOB1, which aid in bringing LATS in contact with the kinase MST1/2. MST1/2 can then phosphorylate and activate LATS1. Upstream core components of the Hippo pathway lay FERM domain proteins Willin/FRMD6 and Merlin/NF2, as well as a protocadherin FAT4 and G-protein-coupled receptor (GPCR) and many other regulators (see Figure). Downstream of LATS1 lay two transcriptional co-activators, YAP and TAZ, which are phosphorylated and inhibited by LATS1, thereby sequestering them in the cytoplasm. Finally, YAP and TAZ have been shown to act through the TEAD/TEF family of transcription factors to modulate the expression of a variety of genes (See Figure). Functionally, the Hippo pathway has been implicated in cell proliferation, apoptosis, the epithelial mesenchymal transition, cell migration, and stem cell differentiation and renewal.

Homology
Mutations
Note
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15688006 | 2005 | The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. | Chan EH et al |
| 25270913 | 2014 | Methylation‑associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma. | Chen KH et al |
| 23985334 | 2013 | Integration of mechanical and chemical signals by YAP and TAZ transcription coactivators. | Guo X et al |
| 18158288 | 2008 | Tumor suppressor LATS1 is a negative regulator of oncogene YAP. | Hao Y et al |
| 16674920 | 2006 | The human tumour suppressor LATS1 is activated by human MOB1 at the membrane. | Hergovich A et al |
| 10831611 | 2000 | Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. | Hirota T et al |
| 12379777 | 2002 | Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma. | Hisaoka M et al |
| 21383157 | 2011 | Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected]. | Ho KC et al |
| 15122335 | 2004 | Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function. | Iida S et al |
| 22909338 | 2012 | Decreased expression of LATS1 is correlated with the progression and prognosis of glioma. | Ji T et al |
| 17049657 | 2006 | Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. | Jiang Z et al |
| 24336504 | 2014 | The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. | Johnson R et al |
| 25041856 | 2014 | TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors. | Kim YH et al |
| 18227151 | 2008 | TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. | Lei QY et al |
| 24682895 | 2014 | Expression of LATS1 contributes to good prognosis and can negatively regulate YAP oncoprotein in non-small-cell lung cancer. | Lin XY et al |
| 25769949 | 2015 | miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1. | Liu S et al |
| 24825474 | 2014 | The Hippo signaling pathway in stem cell biology and cancer. | Mo JS et al |
| 11078797 | 2000 | Molecular analysis of the h-warts/LATS1 gene in human breast cancer. | Morinaga N et al |
| 25628642 | 2014 | New genetic variants of LATS1 detected in urinary bladder and colon cancer. | Saadeldin MK et al |
| 24107629 | 2013 | NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation. | Salah Z et al |
| 22966299 | 2010 | Hypermethylation of the large tumor suppressor genes in Japanese lung cancer. | Sasaki H et al |
| 19885608 | 2009 | Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma. | Steinmann K et al |
| 15746036 | 2005 | Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. | Takahashi Y et al |
| 9988268 | 1999 | Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. | Tao W et al |
| 25119020 | 2015 | Biallelic alterations of the large tumor suppressor 1 (LATS1) gene in infiltrative, but not superficial, basal cell carcinomas in a Japanese patient with nevoid basal cell carcinoma syndrome. | Tate G et al |
| 10528150 | 1999 | The role of lats in cell cycle regulation and tumorigenesis. | Turenchalk GS et al |
| 20935475 | 2010 | LATS tumor suppressor: a new governor of cellular homeostasis. | Visser S et al |
| 23885148 | 2013 | Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation. | Wierzbicki PM et al |
| 25841306 | 2015 | Expression of LATS family proteins in ovarian tumors and its significance. | Xu B et al |
| 11641775 | 2001 | Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G(2)/M arrest or apoptosis. | Yang X et al |
| 15220930 | 2004 | LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. | Yang X et al |
| 23573293 | 2013 | WWP1 E3 ligase targets LATS1 for ubiquitin-mediated degradation in breast cancer cells. | Yeung B et al |
| 23431053 | 2013 | The Hippo pathway: regulators and regulations. | Yu FX et al |
| 22863277 | 2012 | Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. | Yu FX et al |
| 18328423 | 2008 | The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals. | Zeng Q et al |
| 18413746 | 2008 | Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway. | Zhang J et al |
| 25618271 | 2014 | Up-regulation of ITCH is associated with down-regulation of LATS1 during tumorigenesis and progression of cervical squamous cell carcinoma. | Zhou Y et al |
Other Information
Locus ID:
NCBI: 9113
MIM: 603473
HGNC: 6514
Ensembl: ENSG00000131023
Variants:
dbSNP: 9113
ClinVar: 9113
TCGA: ENSG00000131023
COSMIC: LATS1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38277019 | 2024 | LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization. | 0 |
| 38372068 | 2024 | m(6)A-induced TRIB3 regulates Hippo pathway through interacting with LATS1 to promote the progression of lung adenocarcinoma. | 0 |
| 38277019 | 2024 | LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization. | 0 |
| 38372068 | 2024 | m(6)A-induced TRIB3 regulates Hippo pathway through interacting with LATS1 to promote the progression of lung adenocarcinoma. | 0 |
| 36803368 | 2023 | WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein. | 3 |
| 37151881 | 2023 | S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development. | 4 |
| 36803368 | 2023 | WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein. | 3 |
| 37151881 | 2023 | S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development. | 4 |
| 34954927 | 2022 | Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway. | 5 |
| 35027733 | 2022 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1. | 11 |
| 35142365 | 2022 | The clinicopathological and prognostic significances of LATS1 expression in breast cancer. | 0 |
| 35271888 | 2022 | HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP. | 14 |
| 35859006 | 2022 | LATS kinases and SLUG regulate the transition to advanced stage in aggressive oral cancer cells. | 0 |
| 35986120 | 2022 | Identification of a novel LATS1 variant associated with familial cerebral cavernous malformations in a Chinese family. | 0 |
| 36029506 | 2022 | Expression of LATS1 in head and neck squamous cell carcinoma and its effect on tumor cell proliferation and invasion. | 0 |
Citation
Helena J Janse van Rensburg ; Xiaolong Yang ; Stacy Visser-Grieve
LATS1 (Large Tumor Suppressor 1)
Atlas Genet Cytogenet Oncol Haematol. 2015-07-01
Online version: http://atlasgeneticsoncology.org/gene/41127
