Table 1 Pathway analysis of alterations in metastatic compared to non-metastatic M-Wnt cell lines

From: Metabolic reprogramming underlies metastatic potential in an obesity-responsive murine model of metastatic triple negative breast cancer

Pathway

# genes in set

p-value

Genes (fold difference metM-Wntlung/M-Wnt)

Metabolism

  p53 Pathway

11

8.38E-08

RGS16 (16.93); RRAD (7.2); PROCR (6.82); HIST1H1A (6.5); PVT1 (5.83); JAG2 (4.43); PITPNC1 (3.79); F2R (3.43); PTPRE (3.36); SLC7A11 (3.76); PERP (0.06)

  Glycolysis

14

2.12E-07

ANGPTL4 (44.23); B3GNT3 (10.57); ARTN (8.85); LHPP (8.67); NT5E (7.08); NOL3 (5.09); CHST2 (4.79); VCAN (4.13); LHX9 (3.83); TGFBI (3.57); ENO2 (0.33); RRAGD (0.23); HS6ST2 (0.2); AK3 (0.18)

  Oxidative phosphorylation

2

8.27E-06

PHYH (7.23); BDH2 (0.048)

  MTORC1 signaling

2

2.35E-05

SLC7A11 (3.76); BCAT1 (3.25)

  Upregulated by KRAS

25

0.000100599

ITGBL1 (42.46); IL2RG (39.78); TRAF1 (8.98); MYCN (8.39); ID2 (8.48); IRF8 (7.82); TFPI (7.13); MMD (5.79); PLEK2 (5.6); PLAT (5.36); PPBP (5.22); LAT2 (5.19); PLAU (5.01); SEMA3B (4.47); (4.23); ADAM8 (4.85); GPR124 (3.91); IL33 (0.31); CFHR2 (0.29); GPNMB (0.22); EPB41L3 (0.1); CFH (0.1); PRRX1 (0.05)

  Xenobiotic metabolism

11

0.000237967

PTGES (24.65); ID2 (8.48); IRF8 (7.82); IL1R2 (7.65); NQO1 (7.32); ALDH2 (4.07); FBLN1 (3.92); BCAT1 (3.25); ADH7 (3.21); DDAH2 (0.28); ACOX2 (0.13)

  Adipogenesis

11

0.000412562

ANGPTL4 (44.23); ANGPT2 (11.12); OMD (7.51); LTC4S (6.44); SLC27A1 (5.6); SORBS1 (4.17); SNCG (3.86); REEP6 (3.19) ALDH2 (4.07); PHYH (7.23); EPHX2 (4.14)

  Downregulated by KRAS

9

0.01248066

CD80 (30.95); EDN2 (23.5); CAMK1D (9.74); PRODH (7.29); EDN1 (0.29); SEPP1 (0.29); YPEL1 (0.25); MFSD6 (0.14)

  Peroxisome

4

0.044372468

CRABP2 (59.4); HSD17B11 (10.78); GSTK1 (5.7); EPHX2 (4.14)

EMT

  Epthelial-to-mesenchymal transition

27

4.31E-08

GLIPR1 (484.95); PTHLH (17.58); IL15 (11.62); TRAF1 (8.98); ID2 (8.48); COL6A3 (8.36); MMP2 (7.85); MYL9 (6.18); COL3A1 (5.21); ITGB3 (4.93); VCAN (4.13); CRLF1 (4.03); FBLN1 (3.92); THBS1 (3.79); COL12A1 (3.54); TGFBI (3.57); CTGF (3.32); SGCD (3.41); DAB2 (3.4); ENO2 (0.33); LOXL1 (0.31); CDH11 (0.28); MGP (0.19); TNFRSF11B (0.14); IL6 (0.14); POSTN (0.06); PRRX1 (0.05)

  Apical junction

12

0.000612388

TRAF1 (8.98); MMP2 (7.82); MYL9 (6.18); FYB (4.16); VCAN (4.13); AMIGO1 (3.79); TGFBI (3.57); DMP1 (3.55); MYH9 (3.29); ITGA10 (3.22); CDH11 (0.28); TNFRSF11B (0.14)

  Wnt/β-catenin signaling

2

9.02E-05

JAG1 (5.79); JAG2 (4.43)

  Notch signaling

1

0.000643411

JAG1 (5.79)

  Apical surface

3

0.015807801

IL2RG (39.78); HSPB1 (4.86); RTN4RL1 (3.47)

  TGFβ signaling

4

0.026356895

BCAR3 (11.67); ID2 (8.48); LTBP2 (12.41); THBS1 (3.79)

  Hedgehog Signaling

3

0.044234222

MYH9 (3.29); NRCAM (3.11); NKX6-1 (3.06); UNC5C (0.18)

Inflammation

  Inflammatory response

24

1.35E-08

IFITM1 (58.48); HRH1 (37.46); PCDH7 (31.52); RGS16 (16.93); CXCR6 (16.15); IL15 (11.62); SEMA4D (10.43) AHR (4.53); CALCRL (6.99); CHST2 (4.79); EDN1 (0.29); F3 (3); HAS2 (3.03); IL18R1 (3.92); IL1R1 (4.8); IL6 (0.14); ITGB3 (4.93); LY6E (4.08); PIK3R5 (3.8); PTGER4 (3.74); PTPRE (3.36); SLC7A2 (0.25); STAB1 (3.13); TNFAIP6 (4.14);

  TNFα/NFκB signaling

16

6.42E-07

CD80 (30.95); PHLDA2 (30.38); TRAF1 (8.98); ID2 (8.48); EGR3 (7.59); CXCR7 (6.39); JAG1 (5.79) PLAU (5.01); TNFAIP6 (4.14); PTGER4 (3.74); DUSP2 (3.37); PTPRE (3.36); F3 (3); SLC16A6 (0.32); EDN1 (0.29); IL6 (0.14)

  Allograft rejection

13

4.73E-07

IL2RG (39.78); CD80 (30.95); IL15 (11.62); IRF8 (7.82); IL11 (4.57); FYB (4.16); GCNT1 (3.93); F2R (3.43); BCAT1 (3.25); STAB1 (3.13); IL7 (0.32); ST8SIA4 (0.22); IL6 (0.14)

  IL-2/STAT5 signaling

16

2.15E-05

ENPP1 (26.3); RGS16 (16.93); EOMES (9.57); TRAF1 (8.98); IRF8 (7.82); IL1R2 (7.65); NT5E (7.08); TNFSF11 (6.65); CKAP4 (4.92); IL1RL1 (4.85); AHR (4.53); IL18R1 (3.92); PPAP2A (3.36); IFITM3 (3.05); SPRY4 (0.31); RRAGD (0.23);

  IL-6/JAK/STAT3 signaling

10

0.004519815

IL2RG (39.78); CD38 (10.86); IL1R2 (7.65); ITGB3 (4.93); IL1R1 (4.8); LEPR (4.4); IL18R1 (3.92); PIK3R5 (3.8); IL6 (0.14); IL7 (0.32)

  Interferon γ response

15

0.011933194

P2RY14 (25.26); EPSTI1 (12.98); IL15 (11.62); CD38 (10.86); IRF8 (7.82); ITGB7 (4.82); EIF4E3 (4.5); TNFAIP6 (4.14); LY6E (4.08); APOL6 (3.57); IFITM3 (3.05); IL7 (0.32); ST8SIA4 (0.22); IL6 (0.14); CFH (0.1)

  Coagulation

11

0.018260394

CRIP2 (11.19); MMP2 (7.85); PLAT (5.36); PLAU (5.01); F3 (3); ITGB3 (4.93); THBS1 (3.79); USP11 (0.29); CTSH (0.26); ACOX2 (0.13); CFH (0.1)

Stress response

  Unfolded protein response

1

2.51E-07

ERN1 (3.21)

  UV response

6

4.70E-07

RRAD (7.2); OLFM1 (3.65); ENO2 (0.33); GGH (0.25); CHKA (0.21); IL6 (0.14)

  Apoptosis

12

6.56E-05

HGF (20.52); IGFBP6 (17.67); CD38 (10.86); MMP2 (7.85); EGR3 (7.59); PLAT (5.36); HSPB1 (4.86); F2R (3.43); IFITM3 (3.05); ENO2 (0.33); IL6 (0.14); PMAIP1 (0.12)

Other

  Androgen response

4

2.88E-05

INPP4B (58.08); MAF (5.32); PPAP2A (3.36); SEPP1 (0.29)

  Angiogenesis

5

0.001119122

JAG1 (5.79); COL3A1 (5.21); JAG2 (4.43); VCAN (4.13); POSTN (0.06)

  1. Gene sets were identified using a permutation-based approach to test for enrichment across the univariate statistics of all genes in a set. The count of genes in each set that also surpass univariate criteria (q < 0.001 and FC > 3 or FC < 0.33) are listed. Altered genes were functionally clustered using the Hallmark gene sets in Molecular Signature Database (MSigDB) with a threshold set to p < 0.05. Number of genes reflects number of overlap from significant genes identified from this microarray analysis and those featured in Hallmark gene sets. Fold change in metM-Wntlung compared to M-Wnt are shown in parentheses in the right hand column
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