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Fibronectin and type IV collagen activate ERα AF-1 by c-Src pathway: effect on breast cancer cell motility

Oncogene volume 23, pages 8920–8930 (2004)Cite this article

Abstract

The expression of estrogen receptor alpha (ERα) is generally associated with a less invasive and aggressive phenotype in breast carcinoma. In an attempt to understand the role of ERα in regulating breast cancer cells invasiveness, we have demonstrated that cell adhesion on fibronectin (Fn) and type IV Collagen (Col) induces ERα-mediated transcription and reduces cell migration in MCF-7 and in MDA-MB-231 cell lines expressing ERα. Analysis of deleted mutants of ERα indicates that the transcriptional activation function (AF)-1 is required for ERα-mediated transcription as well as for the inhibition of cell migration induced by cell adhesion on extracellular matrix (ECM) proteins. In addition, the nuclear localization signal region and some serine residues in the AF-1 of the ERα are both required for the regulation of cell invasiveness as we have observed in HeLa cells. It is worth noting that c-Src activation is coincident with adhesion of cells to ECM proteins and that the inhibition of c-Src activity by PP2 or the expression of a dominant-negative c-Src abolishes ERα-mediated transcription and partially reverts the inhibition of cell invasiveness in ERα-positive cancer cells. These findings address the integrated role of ECM proteins and ERα in influencing breast cancer cell motility through a mechanism that involves c-Src and seems not to be related to a specific cell type.

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Abbreviations

AF-1:

estrogen receptor activation function 1

AF-2:

estrogen receptor activation function 2

Col:

type IV collagen

ECM:

extracellular matrix

ERα:

estrogen receptor alpha

ERβ:

estrogen receptor beta

Fn:

fibronectin

ERE:

estrogen-responsive element

c-Src(+):

c-Src

Src(−):

dominant negative of c-Src

References

  • Abbas Abidi SM, Howard EW, Dmytryk JJ and Pento JT . (1997). Clin. Exp. Metast., 15, 432–439.

  • Amundadottir LT and Leder P . (1998). Oncogene, 16, 737–746.

  • Aplin AE and Juliano RL . (1999). J. Cell Sci., 112, 695–706.

  • Arnold SF, Vorojeikina DP and Notides AC . (1995). J. Biol. Chem., 270, 30205–30212.

  • Aronica SM, Kraus WL, Katzenellenbogen BS and Power RF . (1994). Proc. Natl. Acad. Sci. USA, 91, 8517–8521.

  • Bunone G, Briand PA, Miksicek RJ and Picard D . (1996). EMBO J., 15, 2174–2183.

  • Cary LA, Han DC, Polte TR, Hanks SK and Guan JL . (1998). J. Cell Biol., 140, 211–221.

  • Chalbos D, Philips A, Galtier F and Rochefort H . (1993). Endocrinology, 133, 571–576.

  • Chen Q, Kinch MS, Lin TH, Burridge K and Juliano RL . (1994). J. Biol. Chem., 6, 26602–26605.

  • Clark EA and Brugge JS . (1995). Science, 268, 233–239.

  • Couse JF, Curtis SW, Washburn TF, Eddy EM, Schomberg DW and Korach KS . (1995). Biochem. Soc. Trans., 23, 929–935.

  • Crowe DL and Brown TN . (1999). Neoplasia, 1, 368–372.

  • Doerr ME and Jones JI . (1996). J. Biol. Chem., 271, 2443–2447.

  • Feng W, Webb P, Nguyen P, Liu X, Li J, Karin M and Kushner PJ . (2001). Mol. Endocrinol., 15, 32–45.

  • Fraker LD, Halter SA and Forbes JT . (1984). Cancer Res., 44, 5757–5763.

  • Giancotti F and Ruoslahti E . (1999). Science, 285, 1028–1032.

  • Guan JL . (1997). Int. J. Biochem. Cell Biol., 29, 1085–1096.

  • Guy CT, Muthuswamy SK, Cardiff RD, Soriano P and Muller WJ . (1994). Genes Dev., 8, 23–32.

  • Hayashido Y, Lucas A, Rougeot C, Godyna S, Argraves WS and Rochefort H . (1998). Int. J. Cancer, 75, 654–658.

  • Hynes RO . (1990). Fibronectins. Springer: New York.

    Book  Google Scholar 

  • Ignar-Trowbridge DM, Pimentel M, Teng CT, Korach KS and McLachlan JA . (1995). Environ. Health Perspect., 103, 35–38.

  • Irby RB and Yeatman TJ . (2000). Oncogene, 19, 5636–5642.

  • Joel PB, Traish AM and Lannigan DA . (1998). J. Biol. Chem., 273, 13317–13323.

  • Kaplan KB, Swedlow JR, Morgan DO and Varmus HE . (1995). Genes Dev., 9, 1505–1517.

  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D and Chambon P . (1994). Science, 270, 1491–1494.

  • Klemke RL, Leng J, Molander R, Brooks PC, Vuori K and Cheresh DA . (1998). J. Cell Biol., 140, 961–972.

  • Lazennec G, Bresson D, Lucas A, Chauveau C and Vignon F . (2001). Endocrinology, 142, 4120–4130.

  • Lehrer S, O'Shaughnessy J, Song HK, Levine E, Savoretti P, Dalton J, Lipsztein R, Kalnicki S and Bloomer WD . (1989). Mt. Sinai. J. Med., 56, 83–85.

  • Lin TH, Chen Q, Howe A and Juliano RL . (1997). J. Biol. Chem., 272, 8849–8852.

  • Liotta LA, Stracke ML, Aznavoorian SA, Beckner ME and Schiffmann E . (1991). Semin. Cancer Biol., 2, 111–114.

  • Lowell CA, Fumagalli L and Berton G . (1996). J. Cell. Biol., 133, 895–910.

  • Maa MC, Leu TH, McCarley DJ, Schatzman RC and Parsons SJ . (1995). Proc. Natl. Acad. Sci. USA, 92, 6981–6985.

  • McGuire WL . (1986). Cancer Surveys: Hormone Receptors Breast Cancer Vol. 5. Bulbrook RD (ed). Oxford University Press: Oxford, pp. 527–536.

    Google Scholar 

  • Miyamoto S, Teramoto H, Gutkind JS and Yamada KM . (1996). J. Cell Biol., 135, 1633–1642.

  • Morino N, Mimura T, Hamasaki K, Tobe K, Ueki K, Kikuchi K, Takehara K, Kadowaki T, Yazaki Y and Nojima Y . (1995). J. Biol. Chem., 270, 269–273.

  • Muthuswamy SK, Siegel PM, Dankort DL, Webster MA and Muller WJ . (1994). Mol. Cell. Biol., 14, 735–743.

  • Osborne CK, Hobbs K and Clark GM . (1985). Cancer Res., 45, 584–590.

  • Petit V, Boyer B, Lentz D, Turner CE, Thiery JP and Valles AM . (2000). J. Cell Biol., 148, 957–970.

  • Platet N, Cunat S, Chalbos D, Rochefort H and Garcia M . (2000). Mol. Endocrinol., 14, 999–1009.

  • Power RF, Mani SK, Codina J, Conneely OM and O' Malley BW . (1991). Science, 254, 1636–1639.

  • Price JE, Polyzos A, Zhang RD and Daniels LM . (1990). Cancer Res., 50, 717–721.

  • Renshaw MW, Ren XD and Schwartz MA . (1997). EMBO J., 16, 5592–5599.

  • Rochefort H, Platet N, Hayashido Y, Derocq D, Lucas A, Cunat S and Garcia M . (1998). J. Steroid Biochem. Mol. Biol., 65, 163–168.

  • Schaller MD, Hildebrand JD and Parsons JT . (1999). Mol. Cell. Biol., 10, 3489–3505.

  • Schlaepfer DD, Broome MA and Hunter T . (1997). Mol. Cell. Biol., 17, 1702–1713.

  • Schlaepfer DD, Hanks SK, Hunter T and Van der Geer P . (1994). Nature, 372, 786–791.

  • Schlaepfer DD and Hunter T . (1996). Mol. Cell. Biol., 16, 5623–5633.

  • Sheffield LG . (1998). Biochem. Biophys. Res. Commun., 250, 27–31.

  • Suen PW, Ilic D, Caveggion E, Berton G, Damsky CH and Lowell CA . (1999). J. Cell Sci., 112, 4067–4078.

  • Summy JM and Gallick GE . (2003). Cancer Metast. Rev., 22, 337–358.

  • Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S, Lippman ME, Martin GR and Dixon RB . (1992). J. Cell. Physiol., 150, 534–544.

  • Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I and Chambon P . (1989). EMBO J., 8, 1981–1986.

  • Weigel N . (1996). Biochem. J., 319, 657–667.

  • Zhu X and Assoian RK . (1995). Mol. Cell. Biol., 6, 273–282.

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Acknowledgements

We thank Dr Didier Picard for kindly providing XETL, pSG5-HeG0, pSG5-HE15 and pSG5-HE19 plasmids, Dr Joan Brugge for generously providing pCMV-cSrc-K295R, Y527F plasmid, Dr Douglas D Boyd for helpfully providing pcDNA3-c-Src/Y527F plasmid, Dr Deborah A Lannigan for kindly providing pcDNA3/ER-S104/S106/S118/A plasmid and Dr Robert XD Song for helpfully providing hE241G/pCMV plasmid. This work was supported by Grant ‘AIRC 2001’.

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  1. Diego Sisci and Saveria Aquila: These authors contributed equally to this work

Authors and Affiliations

  1. Dipartimento Farmaco-Biologico, Università della Calabria, Arcavacata di Rende, Italy

    Diego Sisci, Saveria Aquila, Emilia Middea, Marcello Maggiolini, Fabrizia Mastroianni & Daniela Montanaro

  2. Dipartimento di Biologia Cellulare, Centro Sanitario, Università della Calabria, Arcavacata di Rende, Cosenza, 87030, Italy

    Mariaelena Gentile & Sebastiano Andò

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  1. Diego Sisci
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Correspondence to Sebastiano Andò.

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Sisci, D., Aquila, S., Middea, E. et al. Fibronectin and type IV collagen activate ERα AF-1 by c-Src pathway: effect on breast cancer cell motility. Oncogene 23, 8920–8930 (2004). https://doi.org/10.1038/sj.onc.1208098

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