TISIDB

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm. Cytoplasm, cytoskeleton, spindle pole. Nucleus. Note=Colocalizes with AURKA at the centrosomes during interphase, early prophase and cytokinesis. Migrates to the spindle poles during mitosis, and to the midbody during cytokinesis. Translocates to the nucleus upon mitotic stress by nocodazole treatment.
Domain	PF00069 Protein kinase domain
Function	Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor 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 LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ.

> Gene Ontology [ TOP ]
Biological Process	GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0000082 G1/S transition of mitotic cell cycle GO:0001701 in utero embryonic development GO:0001824 blastocyst development GO:0001825 blastocyst formation GO:0001826 inner cell mass cell differentiation GO:0001827 inner cell mass cell fate commitment GO:0001828 inner cell mass cellular morphogenesis GO:0001933 negative regulation of protein phosphorylation GO:0006469 negative regulation of protein kinase activity GO:0007067 mitotic nuclear division GO:0008544 epidermis development GO:0009755 hormone-mediated signaling pathway GO:0009913 epidermal cell differentiation GO:0016055 Wnt signaling pathway GO:0018105 peptidyl-serine phosphorylation GO:0018209 peptidyl-serine modification GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0030216 keratinocyte differentiation GO:0033673 negative regulation of kinase activity GO:0035265 organ growth GO:0035329 hippo signaling GO:0042326 negative regulation of phosphorylation GO:0043588 skin development GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0045165 cell fate commitment GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045786 negative regulation of cell cycle GO:0046620 regulation of organ growth GO:0048638 regulation of developmental growth GO:0051348 negative regulation of transferase activity GO:0060070 canonical Wnt signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0071900 regulation of protein serine/threonine kinase activity GO:0071901 negative regulation of protein serine/threonine kinase activity GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0198738 cell-cell signaling by wnt GO:1904029 regulation of cyclin-dependent protein kinase activity GO:1904030 negative regulation of cyclin-dependent protein kinase activity
Molecular Function	GO:0004674 protein serine/threonine kinase activity
Cellular Component	GO:0000922 spindle pole GO:0005819 spindle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04390 Hippo signaling pathway
Reactome	R-HSA-162582: Signal Transduction R-HSA-2028269: Signaling by Hippo

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between LATS2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of LATS2 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of LATS2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.018	0.947
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.199	0.884
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.182	0.867
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.008	0.986
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.208	0.918
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.286	0.916
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.108	0.757
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.161	0.912
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.029	0.986
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.586	0.546
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.725	0.169
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.262	0.009

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of LATS2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	14.3	0	14.3	0.196
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	0	20	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	2.7	8.4	0.12
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	3.4	7.7	0.176
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LATS2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LATS2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LATS2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LATS2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LATS2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LATS2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LATS2
Name	large tumor suppressor kinase 2
Aliases	LATS (large tumor suppressor, Drosophila) homolog 2; LATS, large tumor suppressor, homolog 2 (Drosophila); K ......
Chromosomal Location	13q12.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LATS2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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