Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology

Oncogene volume 24, pages 5668–5675 (2005)Cite this article

Abstract

Embryonic stem (ES) cells have provided a valid model to understand early events of mammalian lineage specification and differentiation, leading to important insights into the mechanisms that control embryogenesis at the molecular and cellular levels. Furthermore, ES cells have recently evoked great scientific interest as ideal candidates for the generation of tissues for transplantation therapies. In this respect, particular attention has been paid to the molecules and signaling pathways triggering ES cell differentiation. The EGF-CFC Cripto protein is a key regulator of ES cells fate. The cripto gene is expressed both in ES cells and during the early phases of embryo development, while, in the adult, it is reactivated in a wide range of epithelial cancers. This review will discuss recent findings on the molecular basis of Cripto signaling in ES cell differentiation, providing an intriguing link between stem cell and tumor biology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Adamson ED, Minchiotti G and Salomon DS . (2002). J. Cell Physiol., 190, 267–278.

  • Adkins HB, Bianco C, Schiffer SG, Rayhorn P, Zafari M, Cheung AE, Orozco O, Olson D, De Luca A, Chen LL, Miatkowski K, Benjamin C, Normanno N, Williams KP, Jarpe M, LePage D, Salomon D and Sanicola M . (2003). J. Clin. Invest., 112, 575–587.

  • Arenas E . (2002). Brain Res. Bull., 57, 795–808.

  • Aubert J, Dunstan H, Chambers I and Smith A . (2002). Nat. Biotechnol., 20, 1240–1245.

  • Bain G, Kitchens D, Yao M, Huettner JE and Gottlieb DI . (1995). Dev. Biol., 168, 342–357.

  • Bianco C, Adkins HB, Wechselberger C, Seno M, Normanno N, De Luca A, Sun Y, Khan N, Kenney N, Ebert A, Williams KP, Sanicola M and Salomon DS . (2002). Mol. Cell. Biol., 22, 2586–2597.

  • Bianco C, Strizzi L, Rehman A, Normanno N, Wechselberger C, Sun Y, Khan N, Hirota M, Adkins H, Williams K, Margolis RU, Sanicola M and Salomon DS . (2003). Cancer Res., 63, 1192–1197.

  • Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS and Isacson O . (2002). Proc. Natl. Acad. Sci. USA, 99, 2344–2349.

  • Boheler KR, Czyz J, Tweedie D, Yang HT, Anisimov SV and Wobus AM . (2002). Circ. Res., 91, 189–201.

  • Castelo-Branco G, Wagner J, Rodriguez FJ, Kele J, Sousa K, Rawal N, Pasolli HA, Fuchs E, Kitajewski J and Arenas E . (2003). Proc. Natl. Acad. Sci. USA, 100, 12747–12752.

  • Chambers I and Smith A . (2004). Oncogene, 23, 7150–7160.

  • Cheng SK, Olale F, Bennett JT, Brivanlou AH and Schier AF . (2003). Genes Dev., 17, 31–36.

  • Chung S, Sonntag KC, Andersson T, Bjorklund LM, Park JJ, Kim DW, Kang UJ, Isacson O and Kim KS . (2002). Eur. J. Neurosci., 16, 1829–1838.

  • Ciccodicola A, Dono R, Obici S, Simeone A, Zollo M and Persico MG . (1989). Embo J., 8, 1987–1991.

  • Colas JF and Schoenwolf GC . (2000). Gene, 255, 205–217.

  • Dell’Era P, Ronca R, Coco L, Nicoli S, Metra M and Presta M . (2003). Circ. Res., 93, 414–420.

  • Ding J, Yang L, Yan YT, Chen A, Desai N, Wynshaw-Boris A and Shen MM . (1998). Nature, 395, 702–707.

  • Dono R, Scalera L, Pacifico F, Acampora D, Persico MG and Simeone A . (1993). Development, 118, 1157–1168.

  • Ebert AD, Wechselberger C, Nees M, Clair T, Schaller G, Martinez-Lacaci I, Wallace-Jones B, Bianco C, Weitzel HK and Salomon DS . (2000). Exp. Cell Res., 257, 223–229.

  • Evans MJ and Kaufman MH . (1981). Nature, 292, 154–156.

  • Gray PC, Harrison CA and Vale W . (2003). Proc. Natl. Acad. Sci. USA, 100, 5193–5198.

  • Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS and Schier AF . (1999). Cell, 97, 121–132.

  • Gurdon JB and Bourillot PY . (2001). Nature, 413, 797–803.

  • Gurdon JB, Dyson S and St Johnston D . (1998). Cell, 95, 159–162.

  • Harrison CA, Gray PC, Vale WW and Robertson DM . (2005). Trends Endocrinol. Metab., 16, 73–78.

  • Hescheler J, Fleischmann BK, Lentini S, Maltsev VA, Rohwedel J, Wobus AM and Addicks K . (1997). Cardiovasc. Res., 36, 149–162.

  • Isacson O, Bjorklund LM and Schumacher JM . (2003). Ann. Neurol., 53 (Suppl 3), S135–S146, discussion S146–8.

  • Johnson SE, Rothstein JL and Knowles BB . (1994). Dev. Dyn., 201, 216–226.

  • Kawasaki H, Mizuseki K, Nishikawa S, Kaneko S, Kuwana Y, Nakanishi S, Nishikawa SI and Sasai Y . (2000). Neuron, 28, 31–40.

  • Kinoshita N, Minshull J and Kirschner MW . (1995). Cell, 83, 621–630.

  • Lee SH, Lumelsky N, Studer L, Auerbach JM and McKay RD . (2000). Nat. Biotechnol., 18, 675–679.

  • Liguori GL, Echevarria D, Improta R, Signore M, Adamson E, Martinez S and Persico MG . (2003). Dev. Biol., 264, 537–549.

  • Lindvall O, Kokaia Z and Martinez-Serrano A . (2004). Nat. Med., 10 (Suppl), S42–S50.

  • Loebel DA, Watson CM, De Young RA and Tam PP . (2003). Dev. Biol., 264, 1–14.

  • Maltsev VA, Rohwedel J, Hescheler J and Wobus AM . (1993). Mech. Dev., 44, 41–50.

  • Martin GR . (1981). Proc. Natl. Acad. Sci. USA, 78, 7634–7638.

  • Minchiotti G, Manco G, Parisi S, Lago CT, Rosa F and Persico MG . (2001). Development, 128, 4501–4510.

  • Minchiotti G, Parisi S, Liguori G, Signore M, Lania G, Adamson ED, Lago CT and Persico MG . (2000). Mech. Dev., 90, 133–142.

  • Mizuseki K, Sakamoto T, Watanabe K, Muguruma K, Ikeya M, Nishiyama A, Arakawa A, Suemori H, Nakatsuji N, Kawasaki H, Murakami F and Sasai Y . (2003). Proc. Natl. Acad. Sci. USA, 100, 5828–5833.

  • Monzen K, Hiroi Y, Kudoh S, Akazawa H, Oka T, Takimoto E, Hayashi D, Hosoda T, Kawabata M, Miyazono K, Ishii S, Yazaki Y, Nagai R and Komuro I . (2001). J. Cell Biol., 153, 687–698.

  • Munoz-Sanjuan I and Brivanlou AH . (2002). Nat. Rev. Neurosci., 3, 271–280.

  • Olson EN and Srivastava D . (1996). Science, 272, 671–676.

  • Parish CL, Parisi S, Persico MG, Arenas E and Minchiotti G . (2005). Stem Cells, 23, 471–476.

  • Parisi S, D’Andrea D, Lago CT, Adamson ED, Persico MG and Minchiotti G . (2003). J. Cell Biol., 163, 303–314.

  • Persico MG, Liguori GL, Parisi S, D’Andrea D, Salomon DS and Minchiotti G . (2001). Biochim. Biophys. Acta, 1552, 87–93.

  • Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T and De Robertis EM . (1999). Nature, 397, 707–710.

  • Reissmann E, Jornvall H, Blokzijl A, Andersson O, Chang C, Minchiotti G, Persico MG, Ibanez CF and Brivanlou AH . (2001). Genes Dev., 15, 2010–2022.

  • Rosa FM . (2002). Sci. STKE, 2002, PE47.

  • Rossi F and Cattaneo E . (2002). Nat. Rev. Neurosci., 3, 401–409.

  • Salomon DS, Bianco C and De Santis M . (1999). Bioassays, 21, 61–70.

  • Schiffer SG, Foley S, Kaffashan A, Hronowski X, Zichittella AE, Yeo CY, Miatkowski K, Adkins HB, Damon B, Whitman M, Salomon D, Sanicola M and Williams KP . (2001). J. Biol. Chem., 276, 37769–37778.

  • Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA and Benvenisty N . (2000). Proc. Natl. Acad. Sci. USA, 97, 11307–11312.

  • Shen MM . (2003). J. Clin. Invest., 112, 500–502.

  • Shen MM and Schier AF . (2000). Trends Genet., 16, 303–309.

  • Shen MM, Wang H and Leder P . (1997). Development, 124, 429–442.

  • Shi S and Stanley P . (2003). Proc. Natl. Acad. Sci. USA, 100, 5234–5239.

  • Smith AG . (2001). Annu. Rev. Cell. Dev. Biol., 17, 435–462.

  • Sonntag KC, Simantov R, Bjorklund L, Cooper O, Pruszak J, Kowalke F, Gilmartin J, Ding J, Hu YP, Shen MM and Isacson O . (2005). Mol. Cell Neurosci., 28, 417–429.

  • Strizzi L, Bianco C, Normanno N, Seno M, Wechselberger C, Wallace-Jones B, Khan NI, Hirota M, Sun Y, Sanicola M and Salomon DS . (2004). J. Cell Physiol., 201, 266–276.

  • Thiery JP . (2003). Curr. Opin. Cell Biol., 15, 740–746.

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS and Jones JM . (1998). Science, 282, 1145–1147.

  • Tropepe V, Hitoshi S, Sirard C, Mak TW, Rossant J and van der Kooy D . (2001). Neuron, 30, 65–78.

  • Vallier L, Reynolds D and Pedersen RA . (2004). Dev. Biol., 275, 403–421.

  • Watanabe K, Kamiya D, Nishiyama A, Katayama T, Nozaki S, Kawasaki H, Watanabe Y, Mizuseki K and Sasai Y . (2005). Nat. Neurosci., 8, 288–296.

  • Wechselberger C, Ebert AD, Bianco C, Khan NI, Sun Y, Wallace-Jones B, Montesano R and Salomon DS . (2001). Exp. Cell Res., 266, 95–105.

  • Xu C, Liguori G, Adamson ED and Persico MG . (1998). Dev. Biol., 196, 237–247.

  • Xu C, Liguori G, Persico MG and Adamson ED . (1999). Development, 126, 483–494.

  • Yeo C and Whitman M . (2001). Mol. Cell, 7, 949–957.

  • Ying QL, Stavridis M, Griffiths D, Li M and Smith A . (2003). Nat. Biotechnol., 21, 183–186.

  • Zhang J, Talbot WS and Schier AF . (1998). Cell, 92, 241–251.

Download references

Acknowledgements

Financial support was obtained from Associazione Italiana Ricerca sul Cancro (AIRC) and Ministero Istruzione Università e Ricerca (MIUR). I thank Dr Graziella Persico for stimulating discussion and for her continuous support during all these years. I also thank Dr Silvia Parisi for her invaluable work and all the members of the laboratory for useful discussion and Anna Aliperti for proofreading the manuscript.

Author information

Authors and Affiliations

  1. Institute of Genetics and Biophysics ‘A Buzzati-Traverso’, CNR, Via Pietro Castellino 111, Naples, 80131, Italy

    Gabriella Minchiotti

Authors
  1. Gabriella Minchiotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriella Minchiotti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Minchiotti, G. Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology. Oncogene 24, 5668–5675 (2005). https://doi.org/10.1038/sj.onc.1208917

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208917

Keywords

This article is cited by

Search

Advanced search

Quick links