GLI1 regulates a novel neuropilin-2/α6β1 integrin based autocrine pathway that contributes to breast cancer initiation

EMBO Molecular Medicine

Volumn 5, Issue 4, 2013, Pages 488-508

  Goel, Hira Lal ^a   Pursell, Bryan ^a   Chang, Cheng ^a   Shaw, Leslie M ^a   Mao, Junhao ^a   Simin, Karl ^a   Kumar, Prashant ^a   Vander Kooi, Craig W ^b   Shultz, Leonard D ^c   Greiner, Dale L ^a   Norum, Jens Henrik ^d   Toftgard, Rune ^d   Kuperwasser, Charlotte ^e   Mercurio, Arthur M ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c JACKSON LABORATORY   (United States)

^d KAROLINSKA INSTITUTE   (Sweden)

^e TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Breast cancer; GLI1; Integrin; Neuropilin 2; Stem cells

Indexed keywords

BMI1 PROTEIN; FOCAL ADHESION KINASE; MITOGEN ACTIVATED PROTEIN KINASE; NEUROPILIN 2; PROTEIN; RAS PROTEIN; TRANSCRIPTION FACTOR GLI1; VASCULOTROPIN RECEPTOR; VERY LATE ACTIVATION ANTIGEN 6;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOCRINE EFFECT; BREAST CANCER; BREAST CARCINOGENESIS; CANCER STEM CELL; CELL FUNCTION; CONTROLLED STUDY; ENZYME ACTIVATION; FEMALE; HUMAN; HUMAN TISSUE; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; TRIPLE NEGATIVE BREAST CANCER;

ANIMALS; AUTOCRINE COMMUNICATION; BREAST NEOPLASMS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTEGRIN ALPHA6BETA1; MICE; MICE, INBRED NOD; MICE, TRANSGENIC; MITOGEN-ACTIVATED PROTEIN KINASE 7; NEOPLASTIC STEM CELLS; NEUROPILIN-2; TRANSCRIPTION FACTORS;

EID: 84875804419     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201202078     Document Type: Article

References (87)

1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983-3988
2. Baccelli I, Trumpp A (2012) The evolving concept of cancer and metastasis stem cells. J Cell Biol 198: 281-293
3. Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, Mercurio AM (2001) Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res 61: 5736-5740
4. Bachelder RE, Wendt MA, Mercurio AM (2002) Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res 62: 7203-7206
5. Bachelder RE, Lipscomb EA, Lin X, Wendt MA, Chadborn NH, Eickholt BJ, Mercurio AM (2003) Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res 63: 5230-5233
6. Bae D, Lu S, Taglienti CA, Mercurio AM (2008) Metabolic stress induces the lysosomal degradation of neuropilin-1 but not neuropilin-2. J Biol Chem 283: 28074-28080
7. Bagri A, Tessier-Lavigne M, Watts RJ (2009) Neuropilins in tumor biology. Clin Cancer Res 15: 1860-1864
8. Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, Bouchier-Hayes DJ, Harmey JH (2005) A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells. Br J Cancer 92: 328-333
9. Bates RC, Goldsmith JD, Bachelder RE, Brown C, Shibuya M, Oettgen P, Mercurio AM (2003) Flt-1 (VEGFR-1)-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids. Curr Biol 13: 1721-1727
10. Beck B, Driessens G, Goossens S, Youssef KK, Kuchnio A, Caauwe A, Sotiropoulou PA, Loges S, Lapouge G, Candi A, et al (2011) A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature 478: 399-403
11. Cao Y, Wang L, Nandy D, Zhang Y, Basu A, Radisky D, Mukhopadhyay D (2008) Neuropilin-1 upholds dedifferentiation and propagation phenotypes of renal cell carcinoma cells by activating Akt and sonic hedgehog axes. Cancer Res 68: 8667-8672
12. Castro-Rivera E, Ran S, Thorpe P, Minna JD (2004) Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci USA 101: 11432-11437
13. Caunt M, Mak J, Liang WC, Stawicki S, Pan Q, Tong RK, Kowalski J, Ho C, Reslan HB, Ross J, et al (2008) Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell 13: 331-342
14. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17: 165-172
15. DiMeo TA, Anderson K, Phadke P, Fan C, Perou CM, Naber S, Kuperwasser C (2009) A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer. Cancer Res 69: 5364-5373
16. Ferrara N (2005) VEGF as a therapeutic target in cancer. Oncology 69: 11-16
17. Fiaschi M, Rozell B, Bergstrom A, Toftgard R (2009) Development of mammary tumors by conditional expression of GLI1. Cancer Res 69: 4810-4817
18. Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 10: R25
19. Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, Kuperwasser C (2010) Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci USA 107: 21737-21742
20. Friedrichs K, Ruiz P, Franke F, Gille I, Terpe HJ, Imhof BA (1995) High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res 55: 901-906
21. Geretti E, Shimizu A, Klagsbrun M (2008) Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis 11: 31-39
22. Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, et al (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 120: 485-497
23. Glinka Y, Mohammed N, Subramaniam V, Jothy S, Prud'homme GJ (2012) Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-kappaB activation and tumor sphere formation. Biochem Biophys Res Commun 425: 775-780
24. Glinsky GV, Berezovska O, Glinskii AB (2005) Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 115: 1503-1521
25. Goel HL, Chang C, Pursell B, Leav I, Lyle S, Xi HS, Hsieh CC, Adisetiyo H, Roy-Burman P, Coleman I, et al (2012a) VEGF/Neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-1R define a novel mechanism of aggressive prostate cancer. Cancer Discov 2: 906-921
26. Goel HL, Pursell B, Standley C, Fogarty K, Mercurio AM (2012b) Neuropilin-2 regulates the ability of the α6β1 integrin to form focal adhesions and signal. J Cell Sci 125: 497-506
27. Gray MJ, Van Buren G, Dallas NA, Xia L, Wang X, Yang AD, Somcio RJ, Lin YG, Lim S, Fan F, et al (2008) Therapeutic targeting of neuropilin-2 on colorectal carcinoma cells implanted in the murine liver. J Natl Cancer Inst 100: 109-120
28. Griffiths CL, Olin JL (2012) Triple negative breast cancer: a brief review of its characteristics and treatment options. J Pharm Pract 25: 319-323
29. Guan JL (2010) Integrin signaling through FAK in the regulation of mammary stem cells and breast cancer. IUBMB Life 62: 268-276
30. Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15: 1010-1012
31. Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C, Lander ES (2011) Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146: 633-644
32. Hamerlik P, Lathia JD, Rasmussen R, Wu Q, Bartkova J, Lee M, Moudry P, Bartek J, Jr., Fischer W, Lukas J, et al (2012) Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J Exp Med 209: 507-520
33. Hillman RT, Feng BY, Ni J, Woo WM, Milenkovic L, Hayden Gephart MG, Teruel MN, Oro AE, Chen JK, Scott MP (2011) Neuropilins are positive regulators of Hedgehog signal transduction. Genes Dev 25: 2333-2346
34. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA (2005) Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7: 469-483
35. Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C (2008) The CD44+/CD24- phenotype is enriched in basal-like breast tumors. Breast Cancer Res 10: R53
36. Hu B, Guo P, Bar-Joseph I, Imanishi Y, Jarzynka MJ, Bogler O, Mikkelsen T, Hirose T, Nishikawa R, Cheng SY (2007) Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 26: 5577-5586
37. Idowu MO, Kmieciak M, Dumur C, Burton RS, Grimes MM, Powers CN, Manjili MH (2012) CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome. Hum Pathol 43: 364-373
38. Jeong H, Ryu YJ, An J, Lee Y, Kim A (2012) Epithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotype. Histopathology 60: E87- E95
39. Kasai K, Inaguma S, Yoneyama A, Yoshikawa K, Ikeda H (2008) SCL/TAL1 interrupting locus derepresses GLI1 from the negative control of suppressor-of-fused in pancreatic cancer cell. Cancer Res 68: 7723-7729
40. Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S, Smith AE, Prat A, Perou CM, Gilmore H, et al (2012) Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci USA 109: 2772-2777
41. Kim J, Jung J, Lee SJ, Lee JS, Park MJ (2012a) Cancer stem-like cells persist in established cell lines through autocrine activation of EGFR signaling. Oncol Lett 3: 607-612
42. Kim J, Villadsen R, Sorlie T, Fogh L, Gronlund SZ, Fridriksdottir AJ, Kuhn I, Rank F, Wielenga VT, Solvang H, et al (2012b) Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity. Proc Natl Acad Sci USA 109: 6124-6129
43. Korkaya H, Liu S, Wicha MS (2011) Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest 121: 3804-3809
44. Kumar P, Mukherjee M, Johnson JP, Patel M, Huey B, Albertson DG, Simin K (2012) Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution. PLoS Genet 8: e1003027
45. Laner-Plamberger S, Kaser A, Paulischta M, Hauser-Kronberger C, Eichberger T, Frischauf AM (2009) Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes. Oncogene 28: 1639-1651
46. Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE, Macswords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB, et al (2010) Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 6: 421-432
47. Lauth M, Toftgard R (2007) Non-canonical activation of GLI transcription factors: implications for targeted anti-cancer therapy. Cell Cycle 6: 2458-2463
48. Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremaslani P, Van Lohuizen M, Marino S (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428: 337-341
49. Li MZ, Elledge SJ (2007) Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC. Nat Methods 4: 251-256
50. Liao MJ, Zhang CC, Zhou B, Zimonjic DB, Mani SA, Kaba M, Gifford A, Reinhardt F, Popescu NC, Guo W, et al (2007) Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity. Cancer Res 67: 8131-8138
51. Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M (2010) Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140: 268-279
52. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66: 6063-6071
53. Luo M, Fan H, Nagy T, Wei H, Wang C, Liu S, Wicha MS, Guan JL (2009) Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells. Cancer Res 69: 466-474
54. Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, Gouvin LM, Sharma VM, Mercurio AM (2010) ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell 17: 319-332
55. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133: 704-715
56. Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, et al (2011) The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem cell-like breast cancer cells in human tumors. J Clin Invest 121: 2723-2735
57. Matsushita A, Gotze T, Korc M (2007) Hepatocyte growth factor-mediated cell invasion in pancreatic cancer cells is dependent on neuropilin-1. Cancer Res 67: 10309-10316
58. McDermott SP, Wicha MS (2010) Targeting breast cancer stem cells. Mol Oncol 4: 404-419
59. Mercurio AM, Bachelder RE, Bates RC, Chung J (2004) Autocrine signaling in carcinoma: VEGF and the alpha6beta4 integrin. Semin Cancer Biol 14: 115-122
60. Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK (2010) CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res 70: 4624-4633
61. Mulholland DJ, Xin L, Morim A, Lawson D, Witte O, Wu H (2009) Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model. Cancer Res 69: 8555-8562
62. Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM (2004) Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol 24: 9726-9735
63. Network TCGA (2012) Comprehensive molecular portraits of human breast tumours. Nature 490: 61-70
64. Neufeld G, Kessler O, Herzog Y (2002) The interaction of neuropilin-1 and neuropilin-2 with tyrosine-kinase receptors for VEGF. Adv Exp Med Biol 515: 81-90
65. Pan Q, Chanthery Y, Liang WC, Stawicki S, Mak J, Rathore N, Tong RK, Kowalski J, Yee SF, Pacheco G, et al (2007) Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11: 53-67
66. Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K (2010) Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 16: 876-887
67. Parker MW, Hellman LM, Xu P, Fried MG, Vander Kooi CW (2010) Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin. Biochemistry 49: 4068-4075
68. Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M (2006) Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 20: 3161-3173
69. Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, et al (2007) Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 104: 4048-4053
70. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140: 62-73
71. Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9: 265-273
72. Rajurkar M, De Jesus-Monge WE, Driscoll DR, Appleman VA, Huang H, Cotton JL, Klimstra DS, Zhu LJ, Simin K, Xu L, et al (2012) The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis. Proc Natl Acad Sci USA 109: E1038- E1047
73. Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, et al (2007) IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117: 3988-4002
74. Schaller MD (2010) Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci 123: 1007-1013
75. Scheel C, Eaton EN, Li SH, Chaffer CL, Reinhardt F, Kah KJ, Bell G, Guo W, Rubin J, Richardson AL, et al (2011) Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 145: 926-940
76. Schober M, Fuchs E (2011) Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-beta and integrin/focal adhesion kinase (FAK) signaling. Proc Natl Acad Sci USA 108: 10544-10549
77. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92: 735-745
78. Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, Kong QL, Xu LH, Zhang X, Liu WL, et al (2009) The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest 119: 3626-3636
79. Stecca B, Ruiz i Altaba A (2009) A GLI1-p53 inhibitory loop controls neural stem cell and tumour cell numbers. EMBO J 28: 663-676
80. Stecca B, Mas C, Clement V, Zbinden M, Correa R, Piguet V, Beermann F, Ruiz IAA (2007) Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci USA 104: 5895-5900
81. Sulpice E, Plouet J, Berge M, Allanic D, Tobelem G, Merkulova-Rainon T (2008) Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity. Blood 111: 2036-2045
82. Uniewicz KA, Fernig DG (2008) Neuropilins: a versatile partner of extracellular molecules that regulate development and disease. Front Biosci 13: 4339-4360
83. Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, Ruiz i Altaba A (2009) Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 1: 338-351
84. Vieira AF, Ricardo S, Ablett MP, Dionisio MR, Mendes N, Albergaria A, Farnie G, Gerhard R, Cameselle-Teijeiro JF, Seruca R, et al (2012) P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in basal-like breast cancer. Stem Cells 30: 854-864
85. Wang Y, Zhe H, Ding Z, Gao P, Zhang N, Li G (2012) Cancer stem cell marker Bmi-1 expression is associated with basal-like phenotype and poor survival in breast cancer. World J Surg 36: 1189-1194
86. Yasuoka H, Kodama R, Tsujimoto M, Yoshidome K, Akamatsu H, Nakahara M, Inagaki M, Sanke T, Nakamura Y (2009) Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression. BMC Cancer 9: 220
87. Yoon SO, Shin S, Mercurio AM (2006) Ras stimulation of E2F activity and a consequent E2F regulation of integrin alpha6beta4 promote the invasion of breast carcinoma cells. Cancer Res 66: 6288-6295