Abstract
A large body of evidence has been accumulated that demonstrates dominant effects of Id proteins on different aspects of cellular growth. Generally, constitutive expression of Id not only blocks cell differentiation but also drives proliferation. In some settings, it is sufficient to render cells immortal or induce oncogenic transformation. The participation of Id proteins in advanced human malignancy, where they are frequently deregulated, has been dramatically bolstered by the recent discovery that Id exert pivotal contributions to many of the essential alterations that collectively dictate malignant growth. Relentless proliferation associated with self-sufficiency in growth signals and insensitivity to growth inhibitory signals, sustained neoangiogenesis, tissue invasiveness and migration capabilities of tumor cells all share dependency on the unlimited availability of Id proteins. It is remarkable that many of these features recapitulate those physiologically propelled by Id proteins to support normal development. We propose that the participation of Id in multiple fundamental traits of cancer may be the basis for unprecedented therapeutic opportunities.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alani RM, Hasskarl J, Grace M, Hernandez MC, Israel MA, Munger K . 1999 Proc. Natl. Acad. Sci. USA 96: 9637–9641
Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC . 1996 Proc. Natl. Acad. Sci. USA 93: 13742–13747
Bain G, Cravatt CB, Loomans C, Alberola-Ila J, Hedrick SM, Murre C . 2001 Nat. Immunol. 2: 165–171
Barone MV, Pepperkok R, Peverali FA, Philipson L . 1994 Proc. Natl. Acad. Sci. USA 91: 4985–4988
Beger C, Pierce LN, Kruger M, Marcusson EG, Robbins JM, Welcsh P, Welch PJ, Welte K, King MC, Barber JR, Wong-Staal F . 2001 Proc. Natl. Acad. Sci. USA 98: 130–135
Belletti B, Prisco M, Morrione A, Valentinis B, Navarro M, Baserga R . 2001 J. Biol. Chem. 276: 13867–13874
Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H . 1990 Cell 61: 49–59
Chen CR, Kang Y, Massague J . 2001 Proc. Natl. Acad. Sci. USA 98: 992–999
Chen H, Weng YC, Schatteman GC, Sanders L, Christy RJ, Christy BA . 1999 Biochem. Biophys. Res. Commun. 256: 614–619
Christy BA, Sanders LK, Lau LF, Copeland NG, Jenkins NA, Nathans D . 1991 Proc. Natl. Acad. Sci. USA 88: 1815–1819
Cooper CL, Brady G, Bilia F, Iscove NN, Quesenberry PJ . 1997 Blood 89: 3155–3165
Deed RW, Hara E, Atherton GT, Peters G, Norton JD . 1997 Mol. Cell. Biol. 17: 6815–6821
Desprez PY, Hara E, Bissell MJ, Campisi J . 1995 Mol. Cell. Biol. 15: 3398–3404
Desprez PY, Lin CQ, Thomasset N, Sympson CJ, Bissell MJ, Campisi J . 1998 Mol. Cell. Biol. 18: 4577–4588
Dyson N . 1998 Genes Dev. 12: 2245–2262
Evan GI, Vousden KH . 2001 Nature 411: 342–348
Florio M, Hernandez MC, Yang H, Shu HK, Cleveland JL, Israel MA . 1998 Mol. Cell. Biol. 18: 5435–5444
Grandori C, Cowley SM, James LP, Eisenman RN . 2000 Annu. Rev. Cell. Dev. Biol. 16: 653–699
Hanahan D, Weinberg RA . 2000 Cell 100: 57–70
Hara E, Hall M, Peters G . 1997 EMBO J. 16: 332–342
Hara E, Smith R, Parry D, Tahara H, Stone S, Peters G . 1996 Mol. Cell. Biol. 16: 859–867
Hara E, Yamaguchi T, Nojima H, Ide T, Campisi J, Okayama H, Oda K . 1994 J. Biol. Chem. 269: 2139–2145
Iavarone A, Garg P, Lasorella A, Hsu J, Israel MA . 1994 Genes Dev. 8: 1270–1284
Ishiguro A, Spirin KS, Shiohara M, Tobler A, Gombart AF, Israel MA, Norton JD, Koeffler HP . 1996 Blood 87: 5225–5231
Israel MA, Hernandez MC, Florio M, Andres-Barquin PJ, Mantani A, Carter JH, Julin CM . 1999 Cancer Res. 59: 1726s–1730s
Jen Y, Manova K, Benezra R . 1997 Dev. Dyn. 208: 92–106
Katzenstein HM, Cohn SL . 1998 Curr. Opin. Oncol. 10: 43–51
Kebebew E, Treseler PA, Duh QY, Clark OH . 2000 Surgery 128: 952–957
Kee BL, Rivera RR, Murre C . 2001 Nat. Immunol. 2: 242–247
Kim D, Peng XC, Sun XH . 1999 Mol. Cell. Biol. 19: 8240–8253
Kleeff J, Ishiwata T, Friess H, Buchler MW, Israel MA, Korc M . 1998 Cancer Res. 58: 3769–3772
Krek W, Ewen ME, Shirodkar S, Arany Z, Kaelin Jr WG, Livingston DM . 1994 Cell 78: 161–172
Langlands K, Down GA, Kealey T . 2000 Cancer Res. 60: 5929–5933
Lasorella A, Iavarone A, Israel MA . 1996 Mol. Cell. Biol. 16: 2570–2578
Lasorella A, Noseda M, Beyna M, Yokota Y, Iavarone A . 2000 Nature 407: 592–598
Lasorella A, Boldrini R, Dominici C, Donfrancesco A, Yokota Y, Inserra A, Iavarone A . 2002 Cancer Res. 62: in press
Lee EY, Hu N, Yuan SS, Cox LA, Bradley A, Lee WH, Herrup K . 1994 Genes Dev. 8: 2008–2021
Lin CQ, Singh J, Murata K, Itahana Y, Parrinello S, Liang SH, Gillett CE, Campisi J, Desprez PY . 2000 Cancer Res. 60: 1332–1340
Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R . 1999 Nature 401: 670–677
Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S . 2001 Nat. Med. 7: 1194–1201
Maris JM, Matthay KK . 1999 J. Clin. Oncol. 17: 2264
Martinsen BJ, Bronner-Fraser M . 1998 Science 281: 988–991
Maruyama H, Kleeff J, Wildi S, Friess H, Buchler MW, Israel MA, Korc M . 1999 Am. J. Pathol. 155: 815–822
Mori S, Nishikawa SI, Yokota Y . 2000 EMBO J. 19: 5772–5781
Morrow MA, Mayer EW, Perez CA, Adlam M, Siu G . 1999 Mol. Immunol. 36: 491–503
Nagata Y, Shoji W, Obinata M, Todokoro K . 1995 Biochem. Biophys. Res. Commun. 207: 916–926
Nagata Y, Todokoro K . 1994 Biochem. Biophys. Res. Commun. 199: 1355–1362
Neuman T, Keen A, Zuber MX, Kristjansson GI, Gruss P, Nornes HO . 1993 Dev. Biol. 160: 186–195
Nickoloff BJ, Chaturvedi V, Bacon P, Qin JZ, Denning MF, Diaz MO . 2000 J. Biol. Chem. 275: 27501–27504
Norton JD . 2000 J. Cell Sci. 113: 3897–3905
Norton JD, Atherton GT . 1998 Mol. Cell. Biol. 18: 2371–2381
Norton JD, Deed RW, Craggs G, Sablitzky F . 1998 Trends Cell Biol. 8: 58–65
Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G, Hara E . 2001 Nature 409: 1067–1070
Polsky D, Young AZ, Busam KJ, Alani RM . 2001 Cancer Res. 61: 6008–6011
Roberts EC, Deed RW, Inoue T, Norton JD, Sharrocks AD . 2001 Mol. Cell. Biol. 21: 524–533
Sablitzky F, Moore A, Bromley M, Deed RW, Newton JS, Norton JD . 1998 Cell Growth Differ. 9: 1015–1024
Schindl M, Oberhuber G, Obermair A, Schoppmann SF, Karner B, Birner P . 2001 Cancer Res. 61: 5703–5706
Sherr CJ . 1996 Science 274: 1672–1677
Slack RS, El-Bizri H, Wong J, Belliveau DJ, Miller FD . 1998 J. Cell. Biol. 140: 1497–1509
Takai N, Miyazaki T, Fujisawa K, Nasu K, Miyakawa I . 2001 Cancer Lett. 165: 185–193
Toma JG, El-Bizri H, Barnabe-Heider F, Aloyz R, Miller FD . 2000 J. Neurosci. 20: 7648–7656
Walterhouse DO, Yoon JW . 1997 Cancer Treat. Res. 92: 3–38
Wang S, Sdrulla A, Johnson JE, Yokota Y, Barres BA . 2001 Neuron 29: 603–614
Weinberg RA . 1995 Cell 81: 323–330
Wice BM, Gordon JI . 1998 J. Biol. Chem. 273: 25310–25319
Yates PR, Atherton GT, Deed RW, Norton JD, Sharrocks AD . 1999 EMBO J. 18: 968–976
Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nichikawa S, Gruss P . 1999 Nature 397: 702–706
Acknowledgements
In preparing this review, we relied in part upon comprehensive reviews cited in the text and apologize for the omission of many important original references. Work in our laboratory is supported by NIH grant RO1-CA85628.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lasorella, A., Uo, T. & Iavarone, A. Id proteins at the cross-road of development and cancer. Oncogene 20, 8326–8333 (2001). https://doi.org/10.1038/sj.onc.1205093
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205093
Keywords
This article is cited by
-
Romidepsin hepatocellular carcinoma suppression in mice is associated with deregulated gene expression of bone morphogenetic protein and Notch signaling pathway components
Molecular Biology Reports (2021)
-
Inhibitor of DNA binding in heart development and cardiovascular diseases
Cell Communication and Signaling (2019)
-
Epigenetic role of the nuclear factor NF-Y on ID gene family in endometrial tissues of women with endometriosis: a case control study
Reproductive Biology and Endocrinology (2019)
-
Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2
Cell Death & Disease (2019)
-
Epigenetic regulation of ID4 in breast cancer: tumor suppressor or oncogene?
Clinical Epigenetics (2018)