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.

  • Original Paper
  • Published:

HOXD3 enhances motility and invasiveness through the TGF-β-dependent and -independent pathways in A549 cells

Oncogene volume 21, pages 798–808 (2002)Cite this article

Abstract

Homeobox genes regulate sets of genes that determine cellular fates in embryonic morphogenesis and maintenance of adult tissue architecture by regulating cellular motility and cell-cell interactions. Our previous studies showed that a specific member, HOXD3, when overexpressed, upregulates integrin β3 expression in human erythroleukemia HEL cells and lung cancer A549 cells, and enhances their motility and invasiveness. We performed a microarray study of over 7075 genes to determine the mechanisms underlying the HOXD3-enhanced motility and invasiveness in A549 cells. RT–PCR-based tracking gene analyses highlighted a set of TGF-β-upregulated genes, which included matrix metalloproteinase-2, syndecan-1, CD44, and TGF-β-induced 68 kDa protein. Exogenous TGF-β also caused this pattern of upregulation in A549 cells and enhanced their migratory and invasive activity, confirming the involvement of TGF-β signaling. However, HOXD3 reduced the expression of TGF-β-independent genes coding for desmosomal components such as desmoglein, desmoplakin and plakoglobin which are known to suppress tumor invasion and metastasis. These results suggest that HOXD3 enhances the invasive and metastatic potential of cancer cells through the TGF-β-dependent and -independent pathways.

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

  • Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN . 1987 Cancer Res. 47: 3239–3245

  • Apiou F, Flagiello D, Cillo C, Malfoy B, Poupon MF, Dutrillaux B . 1996 Cytogenet. Cell Genet. 73: 114–115

  • Borrow J, Shearman AM, Stanton Jr VP, Becher R, Collins T, Williams AJ, Dube I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE . 1996 Nat. Genet. 12: 159–167

  • Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh DA . 1997 J. Cell Biol. 139: 257–264

  • Cillo C, Barba P, Freschi G, Bucciarelli G, Magli MC, Boncinelli E . 1992 Int. J. Cancer 51: 892–897

  • Cillo C . 1994–1995 Invasion Metastasis 14: 38–49

  • Cillo C, Faiella A, Cantile M, Boncinelli E . 1999 Exp. Cell. Res. 248: 1–9

  • Conn IG, Vilela MJ, Garrod DR, Crocker J, Wallace DM . 1990 Br. J. Urol. 65: 176–180

  • De Vita G, Barba P, Odartchenko N, Givel JC, Freschi G, Bucciarelli G, Magli MC, Boncinelli E, Cillo C . 1993 Eur. J. Cancer 29A: 887–893

  • Gehring WJ, Hiromi Y . 1986 Annu. Rev. Genet. 20: 147–173

  • George MD, Vollberg TM, Floyd EE, Stein JP, Jetten AM . 1990 J. Biol. Chem. 265: 11098–11104

  • Graham A, Papalopulu N, Krumlauf R . 1989 Cell 57: 367–378

  • Hamada J, Omatsu T, Okada F, Furuuchi K, Okubo Y, Takahashi Y, Tada M, Miyazaki YJ, Taniguchi Y, Shirato H, Miyasaka K, Moriuchi T . 2001 Int. J. Cancer 93: 516–525

  • Harada T, Shinohara M, Nakamura S, Shimada M, Oka M . 1992 Int. J. Oral. Maxillofac. Surg. 21: 346–349

  • Hidai C, Zupancic T, Penta K, Mikhail A, Kawana M, Quertermous EE, Aoka Y, Fukagawa M, Matsui Y, Platika D, Auerbach R, Hogan BL, Snodgrass R, Quertermous T . 1998 Genes Dev. 12: 21–33

  • Hiraki A, Shinohara M, Ikebe T, Nakamura S, Kurahara S, Garrod DR . 1996 Br. J. Cancer 73: 1491–1497

  • Keski-Oja J, Raghow R, Sawdey M, Loskutoff DJ, Postlethwaite AE, Kang AH, Moses HL . 1988 J. Biol. Chem. 263: 3111–3115

  • Khalil N . 1999 Microbes Infect. 1: 1255–1263

  • Kimelman D, Griffin KJ . 2000 Curr. Opin. Genet. Dev. 10: 350–356

  • Kleinman HK, McGarvey ML, Liotta LA, Robey PG, Tryggvason K, Martin GR . 1982 Biochemistry 21: 6188–6193

  • Kueng W, Silber E, Eppenberger U . 1989 Anal. Biochem. 182: 16–19

  • Lucas C, Fendly BM, Mukku VR, Wong WL, Palladino MA . 1991 Meth. Enzymol. 198: 303–316

  • Lyons RM, Keski-Oja J, Moses HL . 1988 J. Cell Biol. 106: 1659–1665

  • Mark M, Rijli FM, Chambon P . 1997 Pediatr. Res. 42: 421–429

  • Massague J, Chen Y-G . 2000 Genes Dev. 14: 627–644

  • McCaffrey TA, Falcone DJ, Du B . 1992 J. Cell. Physiol. 152: 430–440

  • McGinnis W, Krumlauf R . 1992 Cell 68: 283–302

  • Miyazono K, Olofsson A, Colosetti P, Heldin CH . 1991 EMBO J. 10: 1091–1101

  • Mooradian DL, McCarthy JB, Komanduri KV, Furcht LT . 1992 J. Natl. Cancer Inst. 84: 523–527

  • Moses HL, Serra R . 1996 Curr. Opin. Genet. Dev. 6: 581–586

  • Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB, Sheppard D . 1999 Cell 96: 319–328

  • Nagayasu H, Hamada J, Kawano T, Konaka S, Nakata D, Shibata T, Arisue M, Hosokawa M, Takeichi N, Moriuchi T . 1998 Br. J. Cancer 77: 1371–1377

  • Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy Jr JD . 1996a Nat. Genet. 12: 154–158

  • Nakamura T, Largaespada DA, Shaughnessy Jr JD, Jenkins NA, Copeland NG . 1996b Nat. Genet. 12: 149–153

  • Nakashio T, Narita T, Akiyama S, Kasai Y, Kondo K, Ito K, Takagi H, Kannagi R . 1997 Int. J. Cancer 70: 612–618

  • Negoescu A, Lafeuillade B, Pellerin S, Chambaz EM, Feige JJ . 1995 Exp. Cell Res. 217: 404–409

  • Overall CM, Wrana JL, Sodek J . 1991 J. Biol. Chem. 266: 14064–14071

  • Penta K, Varner JA, Liaw L, Hidai C, Schatzman R, Quertermous T . 1999 J. Biol. Chem. 274: 11101–11109

  • Schultz-Cherry S, Chen H, Mosher DF, Misenheimer TM, Krutzsch HC, Roberts DD, Murphy-Ullrich JE . 1995 J. Biol. Chem. 270: 7304–7310

  • Shinohara M, Hiraki A, Ikebe T, Nakamura S, Kurahara S, Shirasuna K, Garrod DR . 1998 J. Pathol. 184: 369–381

  • Skonier J, Neubauer M, Madisen L, Bennett K, Plowman GD, Purchio AF . 1992 DNA Cell Biol. 11: 511–522

  • Taniguchi Y, Komatsu N, Moriuchi T . 1995 Blood 85: 2786–2794

  • Tiberio C, Barba P, Magli MC, Arvelo F, Le Chevalier T, Poupon MF, Cillo C . 1994 Int. J. Cancer 58: 608–615

  • Tselepis C, Chidgey M, North A, Garrod D . 1998 Proc. Natl. Acad. Sci. USA 95: 8064–8069

  • Yehualaeshet T, O'Connor R, Green-Johnson J, Mai S, Silverstein R, Murphy-Ullrich JE, Khalil N . 1999 Am. J. Pathol. 155: 841–851

  • Yu Q, Stamenkovic I . 2000 Genes Dev. 14: 163–176

Download references

Acknowledgements

The authors wish to thank Ms. Masako Yanome for help in preparing the manuscript. This work was supported by a Grant-in-Aid for Scientific Research (B) and a Grant-in-Aid for Scientific Research on Priority Areas (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan

    Yasumasa J Miyazaki, Jun-ichi Hamada, Mitsuhiro Tada, Keiji Furuuchi, Yoko Takahashi & Tetsuya Moriuchi

  2. Division of Cancer Medicine, Surgical Oncology, Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Yasumasa J Miyazaki, Satoshi Kondo & Hiroyuki Katoh

Authors
  1. Yasumasa J Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun-ichi Hamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsuhiro Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keiji Furuuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroyuki Katoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuya Moriuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-ichi Hamada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyazaki, Y., Hamada, Ji., Tada, M. et al. HOXD3 enhances motility and invasiveness through the TGF-β-dependent and -independent pathways in A549 cells. Oncogene 21, 798–808 (2002). https://doi.org/10.1038/sj.onc.1205126

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205126

Keywords

This article is cited by

Search

Advanced search

Quick links