119 (Phospho)proteomics biomarkers for sunitinib response in RCC b: phosphosites upregulated in sensitive patients (continued) Phosphosite p-value FC Role of corresponding protein in RCC KIT_Y932 n/a n/a The c-KIT receptor is activated by its ligand stem cell factor (SCF) and induces several signal transduction pathways (MAPK, PI3K, AKT) and leads to mast cell activation and secretion of pro-angiogenic cytokines. In RCC, the c-KIT receptor activation induces crosstalk between cancer cells, endothelial cells and mast cells, leading to strengthening of pro-angiogenic signaling104-106. c-KIT receptor is one of the main targets of the multi-kinase inhibitor sunitinib. LRRK2_Y2023 n/a n/a LRRK2 amplification increases MET signaling activation and promotes efficient tumor cell growth and survival in papillary renal cell cancer107. CARS1_Y73 n/a n/a No literature describing a role in RCC. ALB_Y164 n/a n/a A decreased pretreatment serum albumin (ALB) level implies a poor prognosis in RCC patients, with a worse progression free and overall survival108. NPEPL_Y229 n/a n/a No literature describing a role in RCC. CAV1_Y11 n/a n/a CAV1 interacts with the EGFR/RAS/ERK and PI3K/AKT pathways and promotes cell invasion, cell growth and VEGF-A secretion109. NDUFB9_Y118 n/a n/a Seven subunits of the mitochondrial complex I, among which NDUFB9, had downregulated mRNA expression in ccRCC110. SSBP1_Y119 n/a n/a No literature describing a role in RCC. PDK1_Y136 n/a n/a PDK1 mRNA expression is upregulated in RCC compared to normal tissue and is negatively correlated with tumor stage111. In vitro, low expression of PDK1 inhibits proliferation, migration and epithelial mesenchymal transition in RCC112. DNAJC13_ Y1641 n/a n/a No literature describing a role in RCC. F2R_Y420 n/a n/a No literature describing a role in RCC. STAT5A_Y98 n/a n/a Dihydrotestosterone promotes cell proliferation through STAT5 activation in RCC cells113. 4
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