TISIDB

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
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	Podoplanin: Membrane Single-pass type I membrane protein Cell projection, lamellipodium membrane Single-pass type I membrane protein Cell projection, filopodium membrane Single-pass type I membrane protein Cell projection, microvillus membrane Single-pass type I membrane protein Cell projection, ruffle membrane Single-pass type I membrane protein Membrane raft Apical cell membrane Basolateral cell membrane Cell projection, invadopodium Note=Localized to actin-rich microvilli and plasma membrane projections such as filopodia, lamellipodia and ruffles (By similarity). Association to the lipid rafts is required for PDPN-induced epithelial to mesenchymal transition (EMT) (PubMed:21376833). Colocalizes with CD9 in tetraspanin microdomains (PubMed:18541721). Localized at invadopodium adhesion rings in tumor cell. Association to the lipid rafts is essential for PDPN recruitment to invadopodia and ECM degradation (PubMed:25486435). ; SUBCELLULAR LOCATION: 29kDa cytosolic podoplanin intracellular domain: Cytoplasm, cytosol
Domain	PF05808 Podoplanin
Function	Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:17616532, PubMed:18215137, PubMed:17222411). Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN (PubMed:18541721). Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness (PubMed:17046996, PubMed:21376833). Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (PubMed:20962267). In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (By similarity). Through binding with LGALS8 may participate to connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462). In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:15515019). Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (PubMed:25486435). Required for normal lung cell proliferation and alveolus formation at birth (By similarity). Does not function as a water channel or as a regulator of aquaporin-type water channels (PubMed:9651190). Does not have any effect on folic acid or amino acid transport (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0001945 lymph vessel development GO:0001946 lymphangiogenesis GO:0006631 fatty acid metabolic process GO:0006690 icosanoid metabolic process GO:0006692 prostanoid metabolic process GO:0006693 prostaglandin metabolic process GO:0007346 regulation of mitotic cell cycle GO:0007596 blood coagulation GO:0007599 hemostasis GO:0008360 regulation of cell shape GO:0022604 regulation of cell morphogenesis GO:0030168 platelet activation GO:0030323 respiratory tube development GO:0030324 lung development GO:0033559 unsaturated fatty acid metabolic process GO:0036303 lymph vessel morphogenesis GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0048286 lung alveolus development GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051272 positive regulation of cellular component movement GO:0060541 respiratory system development GO:1901987 regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1902806 regulation of cell cycle G1/S phase transition GO:2000045 regulation of G1/S transition of mitotic cell cycle
Molecular Function	-
Cellular Component	GO:0001726 ruffle GO:0005902 microvillus GO:0009897 external side of plasma membrane GO:0030027 lamellipodium GO:0030175 filopodium GO:0031252 cell leading edge GO:0031253 cell projection membrane GO:0031256 leading edge membrane GO:0031258 lamellipodium membrane GO:0031527 filopodium membrane GO:0031528 microvillus membrane GO:0032587 ruffle membrane GO:0098552 side of membrane GO:0098858 actin-based cell projection

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-114604: GPVI-mediated activation cascade R-HSA-109582: Hemostasis R-HSA-139943: PLC-mediated hydrolysis of PIP2 R-HSA-76002: Platelet activation, signaling and aggregation

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PDPN 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

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Literatures describing the relation between PDPN and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23690472	Pleural Malignant Mesothelioma	Immunotherapy target	Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM.

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
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

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Statistical results of PDPN 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	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
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 PDPN 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	-0.654	0.302
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.141	0.445
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.282	0.781
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.481	0.274
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.186	0.442
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.408	0.829
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.218	0.732
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.053	0.963
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.248	0.856
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.929	0.338
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	1.79	0.187
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.143	0.496

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PDPN 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	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	0	2.7	-2.7	1
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	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
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	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDPN. 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	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDPN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDPN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDPN. 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	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PDPN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PDPN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PDPN
Name	podoplanin
Aliases	T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location	1p36.21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PDPN collected from DrugBank database.

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

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