Skip to main content
Log in

CCN5/WISP-2: A micromanager of breast cancer progression

  • Review
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

The gain of plasticity by a subset of cancer cells is a unique but common sequence of cancer progression from epithelial phenotype to mesenchymal phenotype (EMT) that is followed by migration, invasion and metastasis to a distant organ, and drug resistance. Despite multiple studies, it is still unclear how cancer cells regulate plasticity. Recent studies from our laboratory and others’ proposed that CCN5/WISP-2, which is found intracellularly (in the nucleus and cytoplasm) and extracellularly, plays a negative regulator of plasticity. It prevents the EMT process in breast cancer cells as well as pancreatic cancer cells. Multiple genetic insults, including the gain of p53 mutations that accumulate over the time, may perturb CCN5 expression in non-invasive breast cancer cells, which ultimately helps cells to gain invasive phenotypes. Moreover, emerging evidence indicates that several oncogenic lesions such as miR-10b upregulation and activation of TGF-β-signaling can accumulate during CCN5 crisis in breast cancer cells. Collectively, these studies indicate that loss of CCN5 activity may promote breast cancer progression; application of CCN5 protein may represent a novel therapeutic intervention in breast cancer and possibly pancreatic cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Araki S, Eitel JA, Batuello CN, Bijangi-Vishehsaraei K, Xie XJ, Danielpour D, Pollok KE, Boothman DA, Mayo LD (2010) TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J Clin Invest 120:290–302

    Article  PubMed  CAS  Google Scholar 

  • Aylon Y, Oren M (2007) Living with p53, dying of p53. Cell 130:597–600

    Article  PubMed  CAS  Google Scholar 

  • Ballare C, Uhrig M, Bechtold T, Sancho E, Di Domenico M, Migliaccio A, Auricchio F, Beato M (2003) Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells. Mol Cell Biol 23:1994–2008

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Saxena N, Sengupta K, Tawfik O, Mayo MS, Banerjee SK (2003) WISP-2 Gene in Human Breast Cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation. Neoplasia 5:63–73

    PubMed  CAS  Google Scholar 

  • Banerjee S, Sengupta K, Saxena NK, Dhar K, Banerjee SK (2005) Epidermal growth factor induces WISP-2/CCN5 expression in estrogen receptor-{alpha}-positive breast tumor cells through multiple molecular cross-talks. Mol Cancer Res 3:151–162

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Dhar G, Haque I, Kambhampati S, Mehta S, Sengupta K, Tawfik O, Phillips TA, Banerjee SK (2008) CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells. Cancer Res 68:7606–7612

    Article  PubMed  CAS  Google Scholar 

  • Beato M, Chalepakis G, Schauer M, Slater EP (1989) DNA regulatory elements for steroid hormones. J Steroid Biochem 32:737–747

    Article  PubMed  CAS  Google Scholar 

  • Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, Barbosa-Morais NL, Teschendorff AE, Green AR, Ellis IO, Tavare S, Caldas C, Miska EA (2007) MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 8:R214

    Article  PubMed  Google Scholar 

  • Bossi G, Lapi E, Strano S, Rinaldo C, Blandino G, Sacchi A (2006) Mutant p53 gain of function: reduction of tumor malignancy of human cancer cell lines through abrogation of mutant p53 expression. Oncogene 25:304–309

    PubMed  CAS  Google Scholar 

  • Brigstock DR (2003) The CCN family: a new stimulus package. J Endocrinol 178:169–175

    Article  PubMed  CAS  Google Scholar 

  • Bulayeva NN, Wozniak AL, Lash LL, Watson CS (2005) Mechanisms of membrane estrogen receptor-alpha-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line. Am J Physiol Endocrinol Metab 288:E388–E397

    Article  PubMed  CAS  Google Scholar 

  • Cadwell C, Zambetti GP (2001) The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth. Gene 277:15–30

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Croce CM (2006a) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Croce CM (2006b) MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 25:6202–6210

    Article  PubMed  CAS  Google Scholar 

  • Christofori G (2006) New signals from the invasive front. Nature 441:444–450

    Article  PubMed  CAS  Google Scholar 

  • Davies SR, Watkins G, Mansel RE, Jiang WG (2007) Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2, and WISP-3 in human breast cancer. Ann Surg Oncol 14:1909–1918

    Article  PubMed  Google Scholar 

  • Dhar G, Banerjee S, Dhar K, Tawfik O, Mayo MS, Vanveldhuizen PJ, Banerjee SK (2008) Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP-2. Cancer Res 68:4580–4587

    Article  PubMed  CAS  Google Scholar 

  • Dhar G, Mehta S, Banerjee S, Gardner A, McCarty BM, Mathur SC, Campbell DR, Kambhampati S, Banerjee SK (2007a) Loss of WISP-2/CCN5 signaling in human pancreatic cancer: a potential mechanism for epithelial-mesenchymal-transition. Cancer Lett 254:63–70

    Article  PubMed  CAS  Google Scholar 

  • Dhar K, Banerjee S, Dhar G, Sengupta K, Banerjee SK (2007b) Insulin-like growth factor-1 (IGF-1) induces WISP-2/CCN5 via multiple molecular cross-talks and is essential for mitogenic switch by IGF-1 axis in estrogen receptor-positive breast tumor cells. Cancer Res 67:1520–1526

    Article  PubMed  CAS  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  • Farazi TA, Spitzer JI, Morozov P, Tuschl T (2011) miRNAs in human cancer. J Pathol 223:102–115

    Article  PubMed  CAS  Google Scholar 

  • Friend S (1994) p53: a glimpse at the puppet behind the shadow play. Science 265:334–335

    Article  PubMed  CAS  Google Scholar 

  • Fritah A, Redeuilh G, Sabbah M (2006) Molecular cloning and characterization of the human WISP-2/CCN5 gene promoter reveal its upregulation by oestrogens. J Endocrinol 191:613–624

    Article  PubMed  CAS  Google Scholar 

  • Fritah A, Saucier C, De WO, Bracke M, Bieche I, Lidereau R, Gespach C, Drouot S, Redeuilh G, Sabbah M (2008) Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells. Mol Cell Biol 28:1114–1123

    Article  PubMed  CAS  Google Scholar 

  • Gasco M, Shami S, Crook T (2002) The p53 pathway in breast cancer. Breast Cancer Res 4:70–76

    Article  PubMed  CAS  Google Scholar 

  • Gort EH, Van HG, Verlaan I, Groot AJ, Plasterk RH, Shvarts A, Suijkerbuijk KP, Van LT, van der Wall E, Raman V, van Diest PJ, Tijsterman M, Vooijs M (2008) The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2alpha. Oncogene 27:1501–1510

    Article  PubMed  CAS  Google Scholar 

  • Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695

    Article  PubMed  CAS  Google Scholar 

  • Haque I, Banerjee S, Mehta S, De A, Majumder M, Mayo MS, Kambhampati S, Campbell DR, Banerjee SK (2011) Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates MicroRNA-10b via hypoxia-inducible factor-1alpha-TWIST signaling networks in human breast cancer cells. J Biol Chem 286:43475–43485

    Article  PubMed  CAS  Google Scholar 

  • Holbourn KP, Acharya KR, Perbal B (2008) The CCN family of proteins: structure-function relationships. Trends Biochem Sci 33:461–473

    Article  PubMed  CAS  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  PubMed  CAS  Google Scholar 

  • Inadera H, Dong HY, Matsushima K (2002) WISP-2 is a secreted protein and can be a marker of estrogen exposure in MCF-7 cells. Biochem Biophys Res Commun 294:602–608

    Article  PubMed  CAS  Google Scholar 

  • Inadera H, Hashimoto S, Dong HY, Suzuki T, Nagai S, Yamashita T, Toyoda N, Matsushima K (2000) WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. Biochem Biophys Res Commun 275:108–114

    Article  PubMed  CAS  Google Scholar 

  • Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, Morony S, Rubin E, Sarao R, Hojilla CV, Komnenovic V, Kong YY, Schreiber M, Dixon SJ, Sims SM, Khokha R, Wada T, Penninger JM (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440:692–696

    Article  PubMed  CAS  Google Scholar 

  • Jun JI, Lau LF (2011) Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov 10:945–963

    Article  PubMed  CAS  Google Scholar 

  • Kalluri R (2009) EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 119:1417–1419

    Article  PubMed  CAS  Google Scholar 

  • Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  PubMed  CAS  Google Scholar 

  • Kang Y, Massague J (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118:277–279

    Article  PubMed  CAS  Google Scholar 

  • Karagiannis ED, Popel AS (2007) Peptides derived from type I thrombospondin repeat-containing proteins of the CCN family inhibit proliferation and migration of endothelial cells. Int J Biochem Cell Biol

  • Kastan MB (2007) Wild-type p53: tumors can’t stand it. Cell 128:837–840

    Article  PubMed  CAS  Google Scholar 

  • Kastan MB, Berkovich E (2007) p53: a two-faced cancer gene. Nat Cell Biol 9:489–491

    Article  PubMed  CAS  Google Scholar 

  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304–6311

    PubMed  CAS  Google Scholar 

  • Kousteni S, Bellido T, Plotkin LI, O’Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104:719–730

    PubMed  CAS  Google Scholar 

  • Lake AC, Castellot JJ Jr (2003) CCN5 modulates the antiproliferative effect of heparin and regulates cell motility in vascular smooth muscle cells. Cell Commun Signal 1:5

    Article  PubMed  Google Scholar 

  • Levin ER (2002) Cellular functions of plasma membrane estrogen receptors. Steroids 67:471–475

    Article  PubMed  CAS  Google Scholar 

  • Levin ER (2003) Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 17:309–317

    Article  PubMed  CAS  Google Scholar 

  • Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331

    Article  PubMed  CAS  Google Scholar 

  • Liang X (2011) EMT: new signals from the invasive front. Oral Oncol 47:686–687

    Article  PubMed  Google Scholar 

  • Lichy JH, Dalbegue F, Zavar M, Washington C, Tsai MM, Sheng ZM, Taubenberger JK (2000) Genetic heterogeneity in ductal carcinoma of the breast. Lab Invest 80:291–301

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Weinberg RA (2008) MicroRNAs in malignant progression. Cell Cycle 7:570–572

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA (2010) Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28:341–347

    Article  PubMed  CAS  Google Scholar 

  • Majumder M, Banerjee S, Mehta S, De A, Dhar K, Tawfik O, Larson MA, Banerjee SK (2011) Estrogen receptor-alpha is activated in Breast ductal epithelial cells by CCN5 in CCN5-conditional Tri Transgenic mice. 102[102nd Annual American Association of Cancer Research Meeting]. 2011. Philadelphia, PA 19106, AACR. 4-4-0011. Ref Type: Conference Proceeding

  • Manolagas SC, Kousteni S (2001) Perspective: nonreproductive sites of action of reproductive hormones. Endocrinology 142:2200–2204

    Article  PubMed  CAS  Google Scholar 

  • Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56

    Article  PubMed  CAS  Google Scholar 

  • Novitskiy SV, Pickup MW, Gorska AE, Owens P, Chytil A, Aakre M, Wu H, Shyr Y, Moses HL (2011) TGF-beta receptor II loss promotes mammary carcinoma progression by Th17-dependent mechanisms. Cancer Discovery 1:431–441

    Article  Google Scholar 

  • Oren M, Bartek J (2007) The sunny side of p53. Cell 128:826–828

    Article  PubMed  CAS  Google Scholar 

  • Pedram A, Razandi M, Aitkenhead M, Hughes CC, Levin ER (2002) Integration of the non-genomic and genomic actions of estrogen. Membrane-initiated signaling by steroid to transcription and cell biology. J Biol Chem 277:50768–50775

    Article  PubMed  CAS  Google Scholar 

  • Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ (1998) WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci U S A 95:14717–14722

    Article  PubMed  CAS  Google Scholar 

  • Polyak K (2011) Heterogeneity in breast cancer. J Clin Invest 121:3786–3788

    Article  PubMed  CAS  Google Scholar 

  • Radisky DC (2005) Epithelial-mesenchymal transition. J Cell Sci 118:4325–4326

    Article  PubMed  CAS  Google Scholar 

  • Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z, Bissell MJ (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127

    Article  PubMed  CAS  Google Scholar 

  • Ray G, Banerjee S, Saxena NK, Campbell DR, Van VP, Banerjee SK (2005) Stimulation of MCF-7 tumor progression in athymic nude mice by 17beta-estradiol induces WISP-2/CCN5 expression in xenografts: a novel signaling molecule in hormonal carcinogenesis. Oncol Rep 13:445–448

    PubMed  CAS  Google Scholar 

  • Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J (1999) p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 274:32631–32637

    Article  PubMed  CAS  Google Scholar 

  • Rozan LM, El-Deiry WS (2007) p53 downstream target genes and tumor suppression: a classical view in evolution. Cell Death Differ 14:3–9

    Article  PubMed  CAS  Google Scholar 

  • Russo JW, Castellot JJ (2010) CCN5: biology and pathophysiology. J Cell Commun Signal 4:119–130

    Article  PubMed  Google Scholar 

  • Sabbah M, Prunier C, Ferrand N, Megalophonos V, Lambein K, De WO, Nazaret N, Lachuer J, Dumont S, Redeuilh G (2011) CCN5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway. Mol Cell Biol 31:1459–1469

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Harada K, Itatsu K, Ikeda H, Kakuda Y, Shimomura S, Shan RX, Yoneda N, Sasaki M, Nakanuma Y (2010) Epithelial-mesenchymal transition induced by transforming growth factor-{beta}1/Snail activation aggravates invasive growth of cholangiocarcinoma. Am J Pathol 177:141–152

    Article  PubMed  CAS  Google Scholar 

  • Saxena N, Banerjee S, Sengupta K, Zoubine MN, Banerjee SK (2001) Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines. Mol Cell Biochem 228:99–104

    Article  PubMed  CAS  Google Scholar 

  • Schutze N, Noth U, Schneidereit J, Hendrich C, Jakob F (2005) Differential expression of CCN-family members in primary human bone marrow-derived mesenchymal stem cells during osteogenic, chondrogenic and adipogenic differentiation. Cell Commun Signal 3:5

    Article  PubMed  Google Scholar 

  • Sengupta K, Banerjee S, Saxena NK, Banerjee SK (2004) Thombospondin-1 disrupts estrogen-induced endothelial cell proliferation and migration and its expression is suppressed by estradiol. Mol Cancer Res 2:150–158

    PubMed  CAS  Google Scholar 

  • Sengupta K, Banerjee S, Dhar K, Saxena N, Mehta S, Campbell DR, Banerjee SK (2006) WISP-2/CCN5 is involved as a novel signaling intermediate in phorbol ester-protein kinase Cα-mediated breast tumor cell proliferation. Biochemistry 45:10698–10709

    Article  PubMed  CAS  Google Scholar 

  • Shah AN, Gallick GE (2007) Src, chemoresistance and epithelial to mesenchymal transition: are they related? Anticancer Drugs 18:371–375

    Article  PubMed  CAS  Google Scholar 

  • Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538–541

    Article  PubMed  CAS  Google Scholar 

  • Singh G, Singh SK, Konig A, Reutlinger K, Nye MD, Adhikary T, Eilers M, Gress TM, Fernandez-Zapico ME, Ellenrieder V (2010) Sequential activation of NFAT and c-Myc transcription factors mediates the TGF-beta switch from a suppressor to a promoter of cancer cell proliferation. J Biol Chem 285:27241–27250

    Article  PubMed  CAS  Google Scholar 

  • Song H, Hollstein M, Xu Y (2007) p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 9:573–580

    Article  PubMed  CAS  Google Scholar 

  • Song YX, Yue ZY, Wang ZN, Xu YY, Luo Y, Xu HM, Zhang X, Jiang L, Xing CZ, Zhang Y (2011) MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation. Mol Cancer 10:1

    Article  PubMed  CAS  Google Scholar 

  • Steeg PS (2007) Cancer: micromanagement of metastasis. Nature 449:671–673

    Article  PubMed  CAS  Google Scholar 

  • Takahashi E, Nagano O, Ishimoto T, Yae T, Suzuki Y, Shinoda T, Nakamura S, Niwa S, Ikeda S, Koga H, Tanihara H, Saya H (2010) Tumor necrosis factor-alpha regulates transforming growth factor-beta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction. J Biol Chem 285:4060–4073

    Article  PubMed  CAS  Google Scholar 

  • Tarin D, Thompson EW, Newgreen DF (2005) The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res 65:5996–6000

    Article  PubMed  CAS  Google Scholar 

  • Teede HJ (2007) Sex hormones and the cardiovascular system: effects on arterial function in women. Clin Exp Pharmacol Physiol 34:672–676

    Article  PubMed  CAS  Google Scholar 

  • Thiery JP (2003) Cell adhesion in cancer. Comptes Rendus Physique 4:289–304

    Article  CAS  Google Scholar 

  • Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142

    Article  PubMed  CAS  Google Scholar 

  • Trimboli AJ, Fukino K, De BA, Wei G, Shen L, Tanner SM, Creasap N, Rosol TJ, Robinson ML, Eng C, Ostrowski MC, Leone G (2008) Direct evidence for epithelial-mesenchymal transitions in breast cancer. Cancer Res 68:937–945

    Article  PubMed  CAS  Google Scholar 

  • Ventura A, Jacks T (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136:586–591

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310

    Article  PubMed  CAS  Google Scholar 

  • Watson CS, Norfleet AM, Pappas TC, Gametchu B (1999) Rapid actions of estrogens in GH3/B6 pituitary tumor cells via a plasma membrane version of estrogen receptor-alpha. Steroids 64:5–13

    Article  PubMed  CAS  Google Scholar 

  • Watson CS, Bulayeva NN, Wozniak AL, Finnerty CC (2005) Signaling from the membrane via membrane estrogen receptor-alpha: estrogens, xenoestrogens, and phytoestrogens. Steroids 70:364–371

    Article  PubMed  CAS  Google Scholar 

  • Watson CS, Jeng YJ, Kochukov MY (2010) Nongenomic signaling pathways of estrogen toxicity. Toxicol Sci 115:1–11

    Article  PubMed  CAS  Google Scholar 

  • Wehling M (1997) Specific, nongenomic actions of steroid hormones. Annu Rev Physiol 59:365–393

    Article  PubMed  CAS  Google Scholar 

  • Weisz L, Damalas A, Liontos M, Karakaidos P, Fontemaggi G, Maor-Aloni R, Kalis M, Levrero M, Strano S, Gorgoulis VG, Rotter V, Blandino G, Oren M (2007) Mutant p53 enhances nuclear factor kappaB activation by tumor necrosis factor alpha in cancer cells. Cancer Res 67:2396–2401

    Article  PubMed  CAS  Google Scholar 

  • Wiesman KC, Wei L, Baughman C, Russo J, Gray MR, Castellot JJ (2010) CCN5, a secreted protein, localizes to the nucleus. J Cell Commun Signal 4:91–98

    Article  PubMed  Google Scholar 

  • Willis A, Jung EJ, Wakefield T, Chen X (2004) Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes. Oncogene 23:2330–2338

    Article  PubMed  CAS  Google Scholar 

  • Wyckoff MH, Chambliss KL, Mineo C, Yuhanna IS, Mendelsohn ME, Mumby SM, Shaul PW (2001) Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem 276:27071–27076

    Article  PubMed  CAS  Google Scholar 

  • Xiang J, Wu J (2010) Feud or friend? The role of the miR-17-92 cluster in tumorigenesis. Curr Genomics 11:129–135

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939

    Article  PubMed  CAS  Google Scholar 

  • Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG (2010) microRNA, cell cycle, and human breast cancer. Am J Pathol 176:1058–1064

    Article  PubMed  CAS  Google Scholar 

  • Zoubine MN, Banerjee S, Saxena NK, Campbell DR, Banerjee SK (2001) WISP-2: a serum-inducible gene differentially expressed in human normal breast epithelial cells and in MCF-7 breast tumor cells. Biochem Biophys Res Commun 282:421–425

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank members of CRU for reading the manuscript and their helpful discussions. This work is supported by VA Merit Award funds to SB and SKB

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sushanta K. Banerjee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banerjee, S.K., Banerjee, S. CCN5/WISP-2: A micromanager of breast cancer progression. J. Cell Commun. Signal. 6, 63–71 (2012). https://doi.org/10.1007/s12079-012-0158-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-012-0158-2

Keywords

Navigation