PDGFRA
platelet-derived growth factor, alpha-receptor
type III family transmembarne receptor tyrosine kinases (RTK), binds to all PDGF isoforms except PDGF-DD, signaling activates MAPK and RAS pathways [Pubmed]
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role in cancer | oncogene |
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differentiation and development | inhibits differentiation by disrupting nuclear localisation and expression of TTF1 in papillary thyroid cancer [Pubmed]; PDGFRA signaling in progenitor cells promotes beige adipocyte commitment in adipocytes [Pubmed] |
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types of alteration in cancer | activating mutations in exons 12,14 and 18 identified in inflammatory fibroid polyps [Pubmed]; in fusion with multiple partners in haematological malignancies [Pubmed]; recurrent D842V, V561D, N659K, D842_H845del, I843_D846del [Pubmed]; range of activating mutations, amplification, gene fusions identified in breast cancer, GIST, melanoma, glioma [Pubmed] |
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impact of mutation on function | D842V, D842_H845del, S566_E571delinsR result in constitutive, ligand-independent activation [Pubmed] |
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fusion partner | STRN in chronic eosinophilic leukaemia [Pubmed]; ETV6 in chronic eosinophilic leukaemia [Pubmed]; FOXP1 in myeloproliferative neoplasms [Pubmed]; FLP1L1 in myeloproliferative neoplasms [Pubmed] |
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clinical impact | expression correlates with lymph node metastasis in colorectal cancer [Pubmed]; high expression linked to lymph node involvement and recurrence in breast cancer [Pubmed]; germline activating mutations give rise to gastrointestinal stromal tumours (GIST) [Pubmed] |
angiogenesis
overexpression inhibits angiogenesis in xenografts in melanoma [Pubmed]; promotes angiogenesis in endothelial cells [Pubmed]
escaping programmed cell death
overexpression induces apoptosis in melanoma SK-MEL-110 cell line [Pubmed]
proliferative signalling
KD suppresses tumour growth in vitro and in vivo in lung squamous cell carcinoma [Pubmed]
invasion and metastasis
overexpression promotes bone metastasis of xenografts in prostate cancer [Pubmed]; expression is assiociated with lympatic metastases in patients, signaling promotes migration and invasion in papillary thyroid cancer TPC-1, 8305C cell line [Pubmed]; receptor activation drives invadopodia formation, promotes cell migration, and upregulates EMT markers Snail and Snug in thyroid cancer B-CPAP cell line [Pubmed]; activating mutations including Y288C, P345S, V561D and D842V increase cell migration in breast cancer, GIST, melanoma, glioma [Pubmed]
suppression of growth
transient overexpression inhibits growth in vitro and in vivo in melanoma SK-MEL-28, A375, Preyer cell line [Pubmed]