Table 1

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

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↓, TCF4↓ TGFBR2↓

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↓

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.

Yan et al. Genome Biology 2008 9:R53   doi:10.1186/gb-2008-9-3-r53

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