LATS1
LATS1 (Serine/threonine-protein kinase LATS1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Cervical cancer, Breast cancer, Ovarian cancer and 4 more.
Overview
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration.
Open Targets scores its association with cancer at 0.73 (direct and indirect evidence; datatypes literature 0.99, animal model 0.41, genetic association 0.00, somatic mutation 0.87). IntOGen calls it a driver in 6 cohorts (1 activating, 5 loss-of-function), covering Basal Cell Carcinoma, Invasive Breast Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Ovarian Epithelial Tumour, Pancreatic Adenocarcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · LATS1 (Serine/threonine-protein kinase LATS1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Cervical cancer, Breast cancer, Ovarian cancer and 4 more.
- 1 · What it is
LATS1 (Serine/threonine-protein kinase LATS1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Cervical cancer, Breast cancer, Ovarian cancer and 4 more.
- 2 · What goes wrong in cancer
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis.
- 3 · How drugs use it
No product in this corpus aims at LATS1 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:6514 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O95835 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000131023 (association with cancer (MONDO_0004992) 0.73; per-cancer scores at or above 0.5: colorectal cancer 0.53, skin cancer 0.55 (GraphQL API, CC0)); IntOGen LATS1 (driver in 6 cohorts (Act 1, LoF 5); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumour suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle; Midbody; Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body (UniProt). Locus 6q25.1 (HGNC).
- Cervical cancer: IntOGen driver in 2 cohorts (CEAD, CESC)
- Breast cancer: IntOGen driver in 1 cohort (BRCA)
- Ovarian cancer: IntOGen driver in 1 cohort (OVT)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PAAD)
- Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)
- Colorectal cancer: Open Targets association 0.53 with colorectal cancer (MONDO_0005575)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 5 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"LATS1" OR ABSTRACT:"LATS1" OR TITLE:"large tumor suppressor kinase 1" OR ABSTRACT:"large tumor suppressor kinase 1" OR TITLE:"Serine/threonine-protein kinase LATS1" OR ABSTRACT:"Serine/threonine-protein kinase LATS1" OR TITLE:"WARTS" OR ABSTRACT:"WARTS") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about LATS1, not a curated reading list.
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