FGFR4 p.G388R signaling (Homo sapiens)

From WikiPathways

Revision as of 11:16, 30 November 2023 by Ulaganathan (Talk | contribs)
Jump to: navigation, search
52, 4, 5542, 4, 53Elevated Treg/CD8 T cell ratio in the tumor microenvironment (For genotype rs351855-A/A)IL107STAT316Cell Cycle ProgressionSTAT316STAT31CD3344Regulatory T cellSTAT316CD3344STAT31ProliferationTumor cellTumor cellTumor cellTumor cellTumor cellTumor cellTregsTregs55TregsTumor cell5Tregs5Tumor cellCD8 T cell3Tumor cellTumor cellTumor cellCD8 T cell3Tumor cellTumor cellTumor cellIL10STAT31STAT361STAT3616CD8 T cellTumor TIssueLymph NodeProliferationTumor-extrinsic gain-of-function by FGFR4 p.Gly388ArgTumor-intrinsic gain-of-function by FGFR4 p.Gly388ArgTumor Cell


Description

A germline variant rs351855-G/A, FGFR c.1162G>A (p.Gly388Arg), activates the proximal STAT3 signaling pathway. This germline receptor variant FGFR p.Gly388Arg, recruits STAT3 to inner cell membranes, resulting in increased levels of STAT3 tyrosine phosphorylation. This heritable variant-specific signaling pathway enhances both tumor-intrinsic proliferation and tumor-extrinsic immune evasion within the tumor microenvironment. The tumor-intrinsic molecular function is driven by elevated levels of tyrosine-phosphorylated STAT3 in tumor cells, promoting cell division and enhancing proliferation. Meanwhile, the tumor-extrinsic molecular function is influenced by increased levels of tyrosine-phosphorylated STAT3 in regulatory T cells and CD8 T cells. This activates STAT3 signaling pathway predominantly in Tregs and alters the Treg/CD8 T cell ratio in lymphoid organs, thereby limiting immune surveillance within the tumor microenvironment.

Comments

 
A germline variant rs351855-G/A, FGFR c.1162G>A (p.Gly388Arg), activates the proximal STAT3 signaling pathway. This germline receptor variant FGFR p.Gly388Arg, recruits STAT3 to inner cell membranes, resulting in increased levels of STAT3 tyrosine phosphorylation. This heritable variant-specific signaling pathway enhances both tumor-intrinsic proliferation and tumor-extrinsic immune evasion within the tumor microenvironment.
 
The tumor-intrinsic molecular function is driven by elevated levels of tyrosine-phosphorylated STAT3 in tumor cells, promoting cell division and enhancing proliferation. Meanwhile, the tumor-extrinsic molecular function is influenced by increased levels of tyrosine-phosphorylated STAT3 in regulatory T cells and CD8 T cells. This activates STAT3 signaling pathway predominantly in Tregs and alters the Treg/CD8 T cell ratio in lymphoid organs, thereby limiting immune surveillance within the tumor microenvironment.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Kogan D, Grabner A, Yanucil C, Faul C, Ulaganathan VK; ''STAT3-enhancing germline mutations contribute to tumor-extrinsic immune evasion.''; J Clin Invest, 2018 PubMed Europe PMC Scholia
  2. Raskov H, Orhan A, Christensen JP, Gögenur I; ''Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy.''; Br J Cancer, 2021 PubMed Europe PMC Scholia
  3. Ulaganathan VK, Ullrich A; ''Membrane-proximal binding of STAT3 revealed by cancer-associated receptor variants.''; Mol Cell Oncol, 2016 PubMed Europe PMC Scholia
  4. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A; ''Interleukin-10 and the interleukin-10 receptor.''; Annu Rev Immunol, 2001 PubMed Europe PMC Scholia
  5. Ulaganathan VK, Sperl B, Rapp UR, Ullrich A; ''Germline variant FGFR4  p.G388R exposes a membrane-proximal STAT3 binding site.''; Nature, 2015 PubMed Europe PMC Scholia
  6. Shao H, Xu X, Mastrangelo MA, Jing N, Cook RG, Legge GB, Tweardy DJ; ''Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
  7. Yu H, Kortylewski M, Pardoll D; ''Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment.''; Nat Rev Immunol, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134737view22:32, 26 July 2024EweitzOntology Term : 'neoplastic cell' added !
134736view22:31, 26 July 2024EweitzOntology Term : 'CL:0001064' removed !
134683view21:53, 25 July 2024EweitzStandardize font name
134682view21:52, 25 July 2024EweitzModified description
134681view21:51, 25 July 2024EweitzModified description
134680view21:51, 25 July 2024EweitzRemove misplaced description
134679view21:49, 25 July 2024EweitzRemove duplicate comments
134678view21:47, 25 July 2024EweitzSimplify, standardize case
134677view21:45, 25 July 2024EweitzEconomize layout
134676view21:36, 25 July 2024EweitzFix typo, standardize case
129739view01:50, 22 May 2024EweitzOntology Term : 'malignant cell' added !
129738view01:49, 22 May 2024EweitzModified title
128235view18:46, 29 January 2024Khanspersconnected interactions
127764view10:00, 3 December 2023EgonwMade three pathways clickable
127743view11:17, 30 November 2023UlaganathanOntology Term : 'fibroblast growth factor signaling pathway' added !
127742view11:16, 30 November 2023UlaganathanOntology Term : 'regulatory T cell' added !
127741view11:16, 30 November 2023UlaganathanOntology Term : 'effector CD8-positive, alpha-beta T cell' added !
127740view11:16, 30 November 2023UlaganathanOntology Term : 'cancer pathway' added !
127725view17:19, 29 November 2023UlaganathanNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
CD334ProteinP22455 (Uniprot-TrEMBL)
Cell Cycle ProgressionPathwayWP179 (WikiPathways)
IL10GeneProductENSG00000136634 (Ensembl)
IL10ProteinP22301 (Uniprot-TrEMBL)
ProliferationPathwayWP179 (WikiPathways)
STAT3ProteinP40763 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5428"
Personal tools