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Table 1 Signal pathways associated with NF-κB regulons in UM-SCC cells

From: Systems biology-defined NF-κB regulons, interacting signal pathways and networks are implicated in the malignant phenotype of head and neck cancer cell lines differing in p53 status

Tumor type* Pathway p53 P-value Genes§
All subgroups Ephrin receptor signaling W 8.1 × 10-3 ANGPT1↓, CXCL14↓, EFNB1↓, EPHB2↑, EPHB4↓, ITGA2↓, GNA15↓, GNAI2↓, GNB1↓, GNG12↓, IL8↑, PGF
   M 2.3 × 10-3 AKT1↓, ANGPT1↓, AXIN1↑, CXCL14↑, EFNB1↓, GNA15↓, GNAI2↓, GNB2↓, GNB4↓, GNG12↓, ITGA2↓, MAP4K4↓, PGF↓, RASA1↑, RAC2↓, RHOA↓, VEGFC
   W+M 8.9 × 10-4 ANGPT1↓, AXIN1↑, CXCL14↑, EFNB1↓, EPHB2↑, GNAI2↓, GNA15↓, GNG12↓, IL8↑, ITGA2↓, PGF↓, RAC2↓, RHOA↓, VEGFC
  Leukocyte extravasation signaling W 4.4 × 10-2 CD99↓, CLDN7↑, CXCL14↓, CYBA↑, GNAI2↓, ICAM1↑, IL8↑, PRKCQ↓, TIMP2↑, VASP
   M 1.8 × 10-3 ACTN3↓, ACTG2↓, CD99↓, CD44↓, CLDN7↑, CXCL14↑, CYBA↑, GNAI2↓, MMP13↑, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, TIMP2↑, VASP
   W+M 7.9 × 10-5 ACTN3↓, CD99↓, CLDN7↑, CXCL14↑, CYBA↑, GNAI2↓, ICAM1↑, IL8↑, MMP13↑, PIK3R3↑, PLCG2↑, PRKCQ↓, RAC2↓, RHOA↓, TIMP2↑, VASP
  Wnt/β-catenin signaling W 3.2 × 10-2 DKK3↓, GJA1↓, PPP2R5B↓, SFRP1↓, SOX8↓, SOX9↓, TCF4↓, TGFBR2↓, TLE4
   M 3.4 × 10-2 AKT1↓, AXIN1↑, CCND1↑, CD44↓, DKK3↓, SOX9↓, SFRP1↓, TCF4↓, TGFB2↓, TGFBR2
   W+M 2.8 × 10-2 AXIN1↑, CCND1↑, DKK3↓, PPP2R5B↓, SFRP1↓, SOX8↓, SOX9↓, TCF4TGFBR2
  Xenobiotic metabolism signaling W 1.2 × 10-2 ALDH1A3↑, ALDH4A1↓, ALDH5A1↑, FMO3↓, GSTM2↓, IL1A↓, IL6↑, NOS2A↓, NQO1↑, PPARBP↓, PPP2R5B↓, PRKCQ↓, SULT1A3
   M 8.7 × 10-3 ALDH1A2↑, ALDH1A3↑, ALDH3B2↑, CYP1A2↑, CYP3A4↓, EIF2AK3↓, FMO3↓, IL1A↓, IL1B↓, IL6↑, NFE2L2↑, NQO1↑, PIK3R3↑, PPARBP↓, SULT1A3
   W+M 1.6 × 10-3 ALDH1A2↑, ALDH5A1↑, ALDH1A3↑, ALDH3B2↑, CYP3A4↓, FMO3↓, IL1A↓, IL6↑, NOS2A↓, NQO1↑, PIK3R3↑, PPARBP↓, PPP2R5B↓, PRKCQ↓, SULT1A3
  ERK/MAPK signaling W+M 4.2 × 10-2 DUSP4↓, DUSP6↓, ELF3↑, ETS1↓, ITGA2↓, PIK3R3↑, PLCG2↑, PPP2R5B↓, PPARG↑, RAC2
  Inositol phosphate metabolism W+M 1.7 × 10-2 ISYNA1↑, ITPKA↑, NEK2↑, PIK3R3↑, PIM1↑, PLK1↑, PRKCQ↓, PLCD1↓, PLCG2↑, PRKX
  IL-6 signaling W 4.4 × 10-2 IKBKE↑, IL1A↓, IL1R2↓, IL1RN↓, IL6↑, IL8
   M 1.7 × 10-2 IL1A↓, IL1B↓, IL1R2↓, IL6↑, IL6ST↓, TNFRSF1A↓, MAP4K4↓, LBP
  p38 MAPK signaling W 4.8 × 10-2 DUSP10↑, IL1A↓, IL1R2↓, IL1RN↓, MAPKAPK3↓, TGFBR2
   M 3.5 × 10-3 DUSP10↑, IL1A↓, IL1B↓, IL1R2↓, MAPKAPK3↓, PLA2G4B↑, TGFB2↓, TGFBR2↓, TNFRSF1A
Wild-type p53-deficient Cell cycle:G2/M DNA damage W 3.5 × 10-3 CDKN1A↓, PLK1↑, RPS6KA1↓, SFN↓, TOP2A
  checkpoint regulation W+M 1.8 × 10-2 CDKN1A↓, PLK1↑, SFN↓, TOP2A
  Neuregulin signaling W 3.4 × 10-2 ADAM17↓, ITGA2↓, NRG2↓, PDK1↑, PICK1↓, PRKCQ
  PPAR signaling W 3.6 × 10-2 IL1A↓, IL1R2↓, IL1RN↓, IKBKE↑, PPARBP↓, PPARG
  Protein ubiquitination pathway W 3.1 × 10-2 BIRC2↑, CDC20↑, DOC1↓, FBXW7↓, NEDD4L↓, PSMB10↑, SMURF2↓, UBE2H↓, UBE2L6↑, USP6
Mutant p53 GM-CSF signaling M 1.5 × 10-2 AKT1↓, CCND1↑, CFS2↓, ETS1↓, PIK3R3↑, PPP3CC
   W+M 6.0 × 10-3 CCND1↑, CFS2↓, ETS1↓, PIK3R3↑, PIM1↑, PPP3CC
  IGF-1 signaling M 2.0 × 10-3 AKT1↓, CYR61↓, IGFBP2↑, IGFBP3↑, IGFBP6↑, IRS1↑, PIK3R3↑, RASA1↑, SFN
   W+M 3.0 × 10-2 CYR61↓, IGFBP2↑, IGFBP3↑, IGFBP6↑, PIK3R3↑, SFN
  Integrin signaling M 1.3 × 10-3 ACTG2↓, ACTN3↓, AKT1↓, BCAR3↓, DDEF1↓, ITGA2↓, ITGA5↓, ITGB4↓, LAMA3↓, LAMB3↓, LAMC2↓, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, RHOC↓, TSPAN4↓, TSPAN7↑, VASP
   W+M 2.6 × 10-2 ACTN3↓, ITGA2↓, ITGA5↓, ITGA6↓, ITGB4↓, LAMA3↓, LAMB3↓, LAMC2↓, PIK3R3↑, PLCG2↑, RAC2↓, RHOA↓, RHOC↓, VASP
  VEGF signaling M 7.8 × 10-3 ACTG2↓, ACTN3↓, AKT1↓, PGF↓, PIK3R3↑, PLCG2↑, SFN↓, VEGFC
   W+M 3.1 × 10-2 ACTN3↓, PGF↓, PIK3R3↑, PLCG2↑, SFN↓, VEGFC
  NF-κB signaling M 1.7 × 10-2 AKT1↓, BCL10↓, IL1A↓, IL1R2↓, IL1B↓, MALT1↓, MAP4K4↓, PIK3R3↑, PLCG2↑, TNFRSF1A
  SAPK/JNK signaling M 2.0 × 10-2 DUSP4↓, DUSP10↑, EDG5↓, IRS1↑, MAP4K4↓, PIK3R3↑, RAC2↓, SH2D2A↓, ZAK
  1. Shown are signaling pathways associated with NF-κB regulons in UM-SCC cells using IPA 5.0 with a significant enrichment (P < 0.05). *Subgroups with different p53 statuses that are associated with the major signal transduction pathways. The subgroups within each pathway based on p53 status: W refers to five UM-SCC cell lines with wild-type-deficient status; M refers to five UM-SCC cell lines with mutant p53 status; and W+M refers to ten UM-SCC cell lines. Statistical significance of a given pathway (cut off, P < 0.05). §Genes included in the pathway by IPA; up and down arrows indicate up- and down-regulated gene expression with two-fold or more changes.