A Role for STEAP2 in Prostate Cancer Progression

A Role for STEAP2 in Prostate Cancer Progression

Helen Whiteland1 Samantha Spencer-Harty2 Claire Morgan 1 Howard Kynaston3David Hywel Thomas2Pradeep Bose4 Neil Fenn4Paul Lewis1 Spencer Jenkins1,3 Shareen H. Doak1

Institute of Life Science, College of Medicine, Swansea University,Swansea, SA2 8PP, Wales, UK
Department of Cellular Pathology, Singleton Hospital, Abertawe Bro Morgannwg University NHS Trust, Swansea, SA2 8QA Wales, UK
Department of Surgery, Cardiff School of Medicine, Heath Park, Cardiff, CF14 4XW, Wales, UK
Department of Urology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Swansea, SA6 6NL,Wales, UK

Correspondence To:

Dr Shareen H. Doak,

Institute of Life Science

College of Medicine

Swansea University

Singleton Park, Swansea, SA2 8PP, Wales, UK

01792 295388

SupplementaryFigure 1

ECM and adhesion molecules array (Cat# OHS 013)
Cell adhesion molecules:
Transmembrane molecules:
CD44, CDH1 (E-cadherin), HAS1, ICAM1, ITGA1 (integrin a1), ITGA2 (integrin a2 / LFA1?), ITGA2B (integrin a2?), ITGA3 (integrin a3), ITGA4 (integrin a4 / LVA-4), ITGA5 (integrin a5), ITGA6 (integrin a6), ITGA7 (integrin a7), ITGA8 (integrin a8), ITGA9 (integrin a9), ITGA10 (integrin a10), ITGA11 (integrin a11), ITGAL (integrin aL / LFA1a / CD11a), ITGAM (integrin aM), ITGAV (integrin aV), ITGAX (integrin aX), ITGB1 (integrin β1), ITGB2 (integrin β2), ITGB3 (integrin β 3 / CD61), ITGB4 (integrin β4), ITGB5 (integrin β5), ITGB6 (integrin β6), ITGB7 (integrin β7), ITGB8 (integrin β8), MMP14, MMP15, MMP16, MMP17, MMP24, NCAM1, PECAM1, SELE (ELAM-1 / E-selectin), SELL (L-selectin), SELP (P-selectin), SGCE, SPG7, VCAM1.
Cell-cell adhesion:
CD44, CDH1 (E-cadherin), COL11A1, COL14A1, COL19A1, COL6A2, COL8A2, CTNND1 (catenin d1), ICAM1, ITGA8, VCAM1.
Cell-matrix adhesion:
ADAMTS13, CD44, ITGA1 (integrin a1), ITGA2 (integrin a2 / LFA1β), ITGA2B (integrin a2β), ITGA3 (integrin a3), ITGA4 (integrin a4 / LVA-4), ITGA5 (integrin a5), ITGA6 (integrin a6), ITGA7 (integrin a7), ITGA8 (integrin a8), ITGA9 (integrin a9), ITGA10 (integrin a10), ITGA11 (integrin a11), ITGAL (integrin aL / LFA1a / CD11a), ITGAM (integrin aM), ITGAV (integrin aV), ITGAX (integrin aX), ITGB1 (integrin β1), ITGB2 (integrin β2), ITGB3 (integrin β3 / CD61), ITGB4 (integrin β4), ITGB5 (integrin β5), ITGB6 (integrin β6), ITGB7 (integrin β7), ITGB8 (integrin β8), SGCE, SPP1 (OPN / osteopontin), THBS3 (TSP-1).
Other adhesion molecules:
CNTN1, COL11A2, COL12A1, COL15A1, COL16A1, COL18A1 (LOC51695 / endostatin), COL24A1, COL27A1, COL4A3, COL4A6, COL5A1, COL5A3, COL6A1, COL6A3, COL7A1, COL8A1, COL9A1, CSPG2, CTGF, CTNNA1 (catenin a), CTNNB1 (catenin ?), CTNND2 (catenin d2), FN1 (fibronectin-1), KAL1, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1 (laminin B1), LAMB2 (laminin B2), LAMB3 (laminin B3), LAMC1, SPOCK, THBS1 (TSP1), THBS2 (TSP2), THBS4 (TSP4), TNA, TNC, VTN (vitronectin).
Extracellular matrix proteins:
Basement membrane constituents:
COL4A2, COL4A3, COL4A6, COL7A1, COL8A2, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMC1, SPARC.
Collagens and ECM structural constituents:
COL11A1, COL11A2, COL12A1, COL14A1, COL15A1, COL16A1, COL18A1 (LOC51695 / endostatin), COL19A1, COL1A1,
COL24A1, COL27A1, COL4A2, COL4A3, COL4A6, COL5A1, COL5A3, COL6A1, COL6A2, COL6A3, COL7A1, COL8A1, COL8A2, COL9A1, FN1, KAL1, LAMA4.
ECM proteases:
ADAMTS1 (Meth 1), ADAMTS8 (Meth 2), ADAMTS13, MMP1 (collagenase-1), MMP2 (gelatinase A), MMP3 (stromelysin-1), MMP7 (matrilysin), MMP8 (neutrophil collagenase), MMP9 (gelatinase B), MMP10 (stromelysin-2), MMP11 (stromelysin-3), MMP12 (macrophage elastase), MMP13 (collagenase-3), MMP14 (MT1-MMP), MMP15, MMP16, MMP17, MMP20 (enamelysin), MMP24, MMP26, SPG7, TIMP1.
ECM protease inhibitors:
COL4A3, COL6A3, COL7A1, KAL1, SPOCK, THBS1, TIMP1, TIMP2, TIMP3.
Other ECM molecules:
CSPG2, CTGF, ECM1, HAS1, LAMB4, SPP1 (OPN / osteopontin), TGFBI, THBS2, THBS3, THBS4, TNA, TNC, VTN.
WNT signalling array (Cat# OHS 043)
Frizzled-1 signalling pathway:
AXIN1, AXIN2, DIXDC1, DVL1, DVL2, DVL3, FZD10, FZD3, FZD4, FZD6, FZD7, FZD8, FZD9.
Frizzled-2 Signalling Pathway:
WNT1, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, WNT16
Regulation of Wnt receptor signalling pathway:
Negative regulation of Wnt receptor signalling pathway: CXXC4, DKK1, DKK2, DKK3, DKK4, FRZB (FRP-3), FSHB, NLK.
Wnt binding antagonists: SFRP1, SFRP4 (FRP-4), SFRP5.
Other regulators of Wnt signalling: PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, SENP2, TCF7L1.
Regulation of growth and proliferation:
Regulation of growth:
PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, WISP1, WISP2.
Regulation of cell proliferation:
CTBP1, CTBP2, LRP5.
Other genes related to growth and proliferation:
FRAT1, FRAT2.
Regulation of cell cycle:
APC, APC2, CCND1, CCND2, CCND3, FGF4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B.
Regulation of transcription:
Transcription factors:
EP300, FOSL1 (Fra-1), FOXN1, JUN, MYC, PITX2, T (Brachyury), TCF7L1.
Other transcription regulators:
AES (TLE / Groucho), CTNNB1 (catenin ?), CTNNBIP1 (ICAT), LEF1, NLK, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PYGO1, PYGO2, SOX17, TCF7 (Tcf-1), TCF7L2, TLE1, TLE2, TLE3, TLE4, WNT1.
Protein modification activities:
Protein kinase activity:
CSNK1A1, CSNK1A1L, CSNK1D, CSNK1G1, CSNK1G2, CSNK1G3, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, GSK3A (GSKalpha), GSK3B (GSKbeta), MARK4, NLK, WIF1.
Protein phosphatase Type 2A complex:
PPP2CA, PPP2CB, PPP2R1A, PPP2R1B.
Protein ubiquitination:
BTRC (b-TrCP), FBXW11, FBXW2, SHFM3.
Other genes related to Wnt signalling:
BCL9, DAAM1, DAAM2, FZD1, FZD2, FZD5, KREMEN1, KREMEN2, LRP6, NKD1, NKD2, PORCN, RHOU, SLC9A3R1.
BMP/TGFβ array (OHS 035)
TGF-β superfamily cytokines:
TGF-β: TGFB1, TGFB2, TGFB3.
BMP: BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8B, BMP10, BMP15.
GDF: AMH, GDF1, GDF2 (BMP9), GDF3 (Vgr-2), GDF5 (CDMP-1), GDF6, GDF7, GDF8, GDF9, GDF10, GDF11 (BMP11), GDF15, IGF1, IGFBP3, IL6, INHA (inhibin a), INHBA (inhibin BA), IVL (involucrin), LEFTY1, LEFTY2, LTBP1, LTBP2, LTBP4, NODAL, PDGFB, TDGF1.
Activin:
INHA (inhibin a), INHBA (inhibin BA), INHBB (inhibin BB), INHBC (inhibin BC), INHBE, LEFTY1, LEFTY2, NODAL.
Receptors:
ACVR1 (ALK2), ACVR1B (ALK4), ACVR1C, ACVR2, ACVR2B, ACVRL1 (ALK1), AMHR2, BMPR1A (ALK3), BMPR1B (ALK6), BMPR2, ITGB5 (integrin B5), ITGB7 (integrin B7), LTBP1, MAP3K7IP1, NR0B1, STAT1, TGFB1I1, TGFBR1 (ALK5), TGFBR2, TGFBR3, TGFBRAP1.
SMAD: SMAD1 (MADH1), SMAD2 (MADH2), SMAD3 (MADH3), SMAD4 (MADH4), SMAD5 (MADH5), SMAD6 (MADH6), SMAD7 (MADH7), SMAD9 (MADH9).
SMAD target genes:
TGF-β activin-responsive:
CDC25A, CDKN1A (p21WAF1 / p21CIP1), CDKN2B (p15LNK2B), COL1A1, COL1A2, COL3A1, FOS, GSC (goosecoid), IGF1, IGFBP3, IL6, ITGB5 (integrin B5), ITGB7 (integrin B7), IVL (involucrin), JUN, JUNB, MYC, PDGFB, SERPINE 1 (PAI-1), TGFB1I1, TGFB1I4, TGFBI, TGIF, TIMP1.
BMP-responsive:
BGLAP (osteocalcin), DLX2, ID1, ID2, ID3, ID4, JUNB, SMAD6 (MADH6), SOX4, STAT1, TCF8.
Molecules regulating signalling of the TGF-β superfamily:
BAMBI, BMPER, CDKN2B (p15LNK2B), CER1 (cerberus), CHRD (chordin), CST3, ENG (Evi-1), EVI1, FKBP1B, FST (follistatin), GREM1, HIPK2, MAP3K7, NBL1 (DAN), NOG, PLAU (uPA), RUNX1 (AML1), RUNX2, SMURF1, SMURF2, TDGF1.
Adhesion and extracellular molecules (Cat# OHS-013):
Cell adhesion molecules:
BGLAP (osteocalcin), ENG (Evi-1), ITGB5 (integrin B5), ITGB7 (integrin B7), TGFB1I1, TGFBI.
Extracellular matrix structural constituents:
BGLAP (osteocalcin), COL1A1, COL1A2, COL3A1, IVL (involucrin), LTBP1, LTBP2, LTBP4, TGFBI, TIMP1.
Other extracellular molecules:
AMH, BMP1, BMP10, BMP15, BMP2, FST (follistatin), GDF1, GDF10, GDF15, GDF2 (BMP9), GDF3 (Vgr-2), GDF9, GREM1, IGF1, IGFBP3, IL6, INHA (inhibin a), INHBA (inhibin BA), INHBB (inhibin BB), INHBC (inhibin BC), PDGFB, PLAU (uPA),
SERPINE1.
Transcription factors and regulators:
DLX2, EVI1, FOS, GSC (goosecoid), HIPK2, ID1, ID3, ID4, JUN, JUNB, MYC, NR0B1, RUNX1 (AML1), RUNX2, SMAD1 (MADH1), SMAD2 (MADH2), SMAD3 (MADH3), SMAD4 (MADH4), SMAD5 (MADH5), SMAD6 (MADH6), SMAD7 (MADH7), SMAD9 (MADH9), SMURF2, SOX4, STAT1, TCF8 (AREB6), TGFB1I1, TGFB1I4, TGIF.
Genes involved in cellular and developmental processes:
Apoptosis:
CDKN1A (p21WAF1 / p21CIP1), HIPK2, IGFBP3, INHA (inhibin a), INHBA (inhibin BA), STAT1, TDGF1, TGFB1.
Embryonic development:
BMP10, BMP4, GDF11 (BMP11), INHBA (inhibin BA), SMAD3, SMURF1, TDGF1.
Muscle development:
GDF8, GDF9, IGF1, SMAD3.
Neurogenesis:
DLX2, GDF11 (BMP11), GREM1, INHA (inhibin a), INHBA (inhibin BA), NOG.
Reproduction:
AMH, AMHR2, BMP15, FST (follistatin), GDF9, INHA (inhibin a), INHBA (inhibin BA), INHBB (inhibin BB), INHBC (inhibin BC), LEFTY2, NR0B1, TDGF1.
Skeletal development:
BGLAP (osteocalcin), BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8B, BMPR2, CHRD (chordin), COL1A1, COL1A2, GDF10, GDF11 (BMP11), IGF1, INHA (inhibin a), INHBA (inhibin BA), NOG, RUNX2.
Prostate cancer biomarkers array (Cat# OHS 403)
Androgen receptor and associated proteins:
AR, NR1I3, RNF14, SHBG, SRD5A2, TGFB1I1.
Apoptosis:
Induction of apoptosis:
BAK1, BAX, CASP3, CDKN1A, DAPK1, INHA, MAPK1, NOX5, PRKCA, PRKCE, TIMP3, TNFSF10, TP53.
Caspases:
CASP1, CASP3, CASP7.
Anti-apoptosis:
AKT1, BCL2, BCL2L1, IGF1R, IL1A, IL2, NFKB1, PRKCZ, TGFB1, TNF.
Other apoptosis genes:
AGTR2, BRCA1, CLU, E2F1, IGFBP3, IL1B, IL24, NFKBIA, PAWR, VEGF.
Cell cycle:
Cell cycle checkpoint:
BRCA1, CDKN2A, RB1, TP53.
Cell cycle arrest:
CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN3, INHA, MAPK12, MYC, RASSF1, TP53.
Negative regulation of the cell cycle:
APC, BAX, BRCA1, CDKN1C, CDKN2A, CDKN2B, EGFR, ESR1, FHIT, INHA, KLK10, MAPK12, MTSS1, PTEN, RASSF1, RB1, TP53.
Other regulators of the cell cycle:
BCL2, CCND1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, E2F1, FGF1, FGF10, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, HK2, HRAS, IGF1R, IGF2, IL1A, IL1B, MAPK1, MAPK13, MAPK3, MAPK4, MAPK6, MAPK7, PCNA, PRKCA, TGFA, TGFB1, TGFB2, TGFB3, VEGF.
Cell growth and proliferation:
Cytokines:
BMP6, IL12A, IL1A, IL1B, IL2, IL24, INHA, TNF, TNFSF10
Growth factors:
BMP6, EGF, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, GRP, IGF1, IGF2, IL12A, IL1A, IL1B, IL2, INHA, TGFA, TGFB1, TGFB2, TGFB3, VEGF
Positive regulation of cell proliferation:
CDK2, EGF, FGF10, FGF18, FGF2, FGF4, FGF7, IGF1, IGF1R, IL2, VEGF
Negative regulation of cell proliferation:
BCL2, CD164, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN3, GNRH1, IGFBP6, IL1A, IL1B, ODZ1, PAWR, PLG, TGFB1I1
Other regulators of cell growth and proliferation:
AR, BRCA1, CDK3, CDK4, CDK5, CDK6, CDK7, CDK9, E2F1, EGFR, ENO1, ERBB2, ESR1, ESR2, IGFBP3, IGFBP6, IL2, INSL4, MYC, NOX5, NR6A1, PAP, PCNA, PRKCQ, PRKD1, PRL, TP53
Cell differentiation:
FGF22, FGF23, FGF9, IGFBP3, IL2, INHA, KLK6, TP53.
Hormones and related genes:
Hormones:
CHGB, GNRH1, IGF1, IGF2, INHA, INSL3, INSL4, PRL.
Hormone regulators:
KLK6, SHBG.
Thyroid hormone receptors:
NR1D1, NR1H3, NR1I3, NR2F6, NR4A3.
Other steroid hormone receptors:
AR, ESR1, ESR2, NR0B1, NR0B2, NR1D2, NR1H2, NR1H4, NR1I2, NR2C1, NR2C2, NR2E1, NR2E3, NR2F1, NR2F2, NR3C1, NR3C2, NR4A1, NR4A2, NR5A1, NR5A2, NR6A1, PGR, RARB.
Angiogenesis factors:
FGF1, FGF2, FGF6, KLK3, KRT1, VEGF.
Extracellular matrix (ECM):
APOC1, BRCA1, CHGA, CHGB, CLU, COL1A1, COL6A1, EGF, ERBB2, ERK8, FGF1, FGF10, FGF11, FGF13, FGF14, FGF16, FGF17, FGF18, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, GNRH1, IGF1, IGF2, IGFBP3, IGFBP6, IL12A, IL1A, IL1B, IL2, IL24, INHA, INSL3, INSL4, KLK10, KLK12, KLK13, KLK14, KLK15, KLK3, KLK4, KLK5, KLK6, KLK9, MMP2, MMP9, MSMB, NTN4, ODZ1, PAP, PLAU, PRL, PSAP, SERPINA3, SHBG, TGFA, TIMP3, VEGF.
Cell adhesion:
Cell- cell adhesion:
CD44, CDH1, CDH10, CDH19, CDH20, CDH7, CDH9.
Homophilic cell adhesion:
CDH1, CDH10, CDH13, CDH18, CDH19, CDH20, CDH7, CDH8, CDH9, ROBO2.
Cell-matrix adhesion:
CD44, ILK, ITGA1.
Other cell adhesion regulators:
APC, CD164, COL6A1, MTSS1, PAP, TGFB1I1, TNF.
Proteases and inhibitors:
Kallikreins:
KLK1, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9.
Metallopeptidases:
FOLH1, MMP2, MMP9.
Other proteases:
CASP1, CASP3, CASP7, PLAU, PLG.
Protease inhibitors:
SERPINA3, TIMP3.
Protein kinases and inhibitors:
Cyclin-dependent protein kinases:
CDK2, CDK3, CDK4, CDK5, CDK7, CDK9, CDK Inhibitors, AGTR2, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C.
JUN kinases:
MAPK10, MAPK8, MAPK9.
MAP kinases:
ERK8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9.
MAP kinase kinases:
MAPK10, MAPK14.
Protein kinase C members:
PRKCA, PRKCB1, PRKCE, PRKCG, PRKCH, PRKD3.
Janus kinases:
INSL3, TYK2.
Other protein kinases:
AKT1, CDK6, CDK8, DAPK1, EGFR, ERBB2, HK2, HK3, IGF1R, ILK, MAP2K4, MAP3K1, PRKCD, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD2, RNASEL, SRC, TGFA.
Transcription factors and regulators:
Nuclear receptors:
ESR1, ESR2, NR0B1, NR0B2, NR1D1, NR1D2, NR1H2, NR1H3, NR1H4, NR1I2, NR1I3, NR2C1, NR2C2, NR2E1, NR2E3, NR2F1, NR2F2, NR2F6, NR3C1, NR3C2, NR4A1, NR4A2, NR4A3, NR5A1, NR5A2, NR6A1, PGR, RARB.
Other transcription factors and regulators:
AR, BRCA1, CDK7, CDK8, CDK9, E2F1, EGR3, ELL, ENO1, EZH1, EZH2, FGF10, HIF1A, JUN, MYC, NCOA4, NFKB1, NFKBIA, NKX3-1, PAWR, PIAS1, RB1, RNF14, SOX2, TGFB1I1, TNF, TP53, TRPS1.
Genes involved in stress response:
Antibacterial humoral response:
IL12A, IL1B, MAPK11, MAPK14, NFKB1, NR4A2.
Inflammatory response:
IL1A, IL1B, NFKB1, NR3C1, PAP, SERPINA3, TNF.
Other stress response genes:
AKT1, BRCA1, CD164, FGF10, FGF16, FGF7, HIF1A, IL2, IL24, INHA, KLK6, KRT1, MAPK1, MAPK11, MAPK13, MAPK14, MAPK8, MAPK9, NFKB1, NFKBIA, ODZ1, TNF, TNFSF10, TP53, VEGF.
Other prostate cancer markers:
AGR2, AIG1, AKAP1, AKAP2, CANT1, CAV1, CDH12, CLDN3, CLN3, CYB5, CYC1, DAB2IP, DES, DNCL1, ELAC2, ENO2, ENO3, FASN, FLJ12584, FLJ25530, GAGEB1, GAGEC1, GGT1, GSTP1, HIP1, HUMCYT2A, IL29, K6HF, KAI1, KRT2A, MIB1, PART1, PATE, PCA3, PIAS2, PIK3CG, PPID, PR1, PSCA, SLC2A2, SLC33A1, SLC43A1, STEAP, STEAP2, TPM1, TPM2, TRPC6.