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:

Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells

Oncogene volume 22, pages 3297–3306 (2003)Cite this article

Abstract

Thymosin β-4 (Tβ-4), a small peptide originally isolated from calf thymus, modulates the formation of F-actin microfilaments by sequestering the monomeric G-actin. Recent studies have shown that overexpression of the Tβ-4 gene occurs not only in many human carcinomas but also in the highly metastatic melanomas and fibrosarcomas. However, little is known about the specific growth advantages acquired by different tumors from this genetic abnormality. To address the above questions, Tβ-4-overexpressing human colon carcinoma (SW480) cells were established by stable transfection and their phenotypic changes were monitored. We found that both the morphology and the cortical actin cytoskeleton of SW480 cells were altered by Tβ-4 overexpression. Moreover, both cellular level and that distributed over the intercellular junctions of the E-cadherin were decreased in the Tβ-4 overexpressers, which were accompanied by a twofold increase in their saturation densities. Meanwhile, these cells also exhibited an increased ability to form colonies in soft agar. Interestingly, a dramatic increase of growth rate was detected in the Tβ-4 overexpressers, which might be attributed to an accelerated proliferation induced by c-Myc that was activated by nuclear β-catenin. Finally, a motility increase of these cells was demonstrated by two independent migration assays, which was accompanied by an enhanced focal contact. Taken together, our data suggest that the drastic growth property and motility changes of the SW480 cells overexpressing Tβ-4 gene are due mainly to a deregulated cell–cell adhesion arisen from the downregulation of E-cadherin, plus uncontrolled cell proliferation owing to the upregulation of β-catenin, both resulted from a breakdown of actin microfilaments caused by the overexpression of this G-actin sequestering peptide.

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
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Aberle H, Bauer A, Stappert J, Kispert A and Kemler R . (1997). EMBO J., 16, 3797–3804.

  • Angres B, Barth A and Nelson WJ . (1996). J. Cell Biol., 134, 549–557.

  • Assoian RK and Schwartz MA . (2001). Curr. Opin. Genet. Dev., 11, 48–53.

  • Bao LR, Loda M, Janmey PA, Stewart R, Anand-Apte B and Zetter BR (1996) Nat. Med., 2, 1322–1328.

  • Barker N and Clevers H . (2000). Bioessays, 22, 962–965.

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R and Birchmeier W . (1996). Nature, 382, 638–642.

  • Boudreau N, Sympson CJ, Werb Z and Bissell MJ . (1995). Science, 267, 891–893.

  • Brabletz T, Jung A, Dag S, Hlubek F and Kirchner T . (1999). Am. J. Pathol., 155, 1033–1038.

  • Burridge K, Fath K, Kelly T, Nuckolls G and Turner C . (1988). Annu. Rev. Cell Biol., 4, 487–525.

  • Califano D, Monaco C, Santelli G, Giuliano A, Veronese ML, Berlingeri MT, de Franciscis V, Berger N, Trapasso F, Santoro M, Viglietto G and Fusco A . (1998). Cancer Res., 58, 823–828.

  • Cassimeris L, Safer D, Nachmias VT and Zigmond SH . (1992). J. Cell Biol., 119, 1261–1270.

  • Chakravatri A, Zehr EM, Zietman AL, Shipley WU, Goggins WB, Finkelstein DM, Young RH, Chang EL and Wu CL . (2000). Urology, 55, 635–638.

  • Christofori G and Semb H . (1999). Trends Biochem. Sci., 24, 73–76.

  • Clark EA, Golub TR, Lander ES and Hyens RO . (2000). Nature, 406, 532–535.

  • Ezzell RM, Goldmann WH, Wang N, Parasharama N and Ingber DE . (1997). Exp. Cell Res., 231, 14–26.

  • Frisch SM and Francis H . (1994). J. Cell Biol., 124, 619–626.

  • Gold JS, Bao L, Ghoussoub RA, Zetter BR and Rimm DL . (1997). Mol. Pathol., 10, 1106–1112.

  • Golla R, Philip N, Safer D, Chintapalli J, Hoffman R, Collins L and Nhmias VT . (1997). Cell Motil. Cytoskel., 38, 187–200.

  • Gumbiner BM . (1996). Cell, 84, 345–357.

  • Hall AK . (1991). Int. J. Cancer, 48, 672–677.

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW . (1998). Science, 281, 1509–1512.

  • Kobayashi T, Okada F, Fuji N, Tomita N, Ito S, Tazawa H, Aoyama T, Choi SK, Shibata T, Fujita H and Hosokawa M . (2002). Am. J. Pathol., 160, 869–882.

  • Lee SH, Zhang W, Choi JJ, Cho YS, Lee SH, Kim JW, Hu L, Xu J, Liu J and Lee JH . (2001). Oncogene, 20, 6700–6706.

  • Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X and He X . (2002). Cell, 108, 837–847.

  • Low TLK and Goldstein AL . (1982). J. Biol. Chem., 257, 1000–1006.

  • Luna EJ and Hitt AL . (1992). Science, 258, 955–964.

  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destree O and Clevers H . (1996). Cell, 86, 391–399.

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW . (1997). Science, 275, 1787–1790.

  • Nakanishi K, Sakamoto M, Yasuda J, Takamura M, Fujita N, Tsuruo T, Todo S and Hirohashi S . (2002). Cancer Res., 62, 2971–2975.

  • Newell KJ, Witty JP, Rodgers WH and Matrisian LM . (1994). Mol. Carcinogen., 10, 199–206.

  • Pawlak G and Helfman DM . (2001). Curr. Opin. Genes Dev., 11, 41–47.

  • Quigley JP and Armstrong PB . (1998). Cell, 94, 281–284.

  • Quinlan MP and Hyatt JL . (1999). Cell Growth Differ., 10, 839–854.

  • Radeva G, Petroceli T, Behrend E, Leung-Hagesteijn C, Filmus J, Singerland J and Dedhar S . (1997). J. Biol. Chem., 272, 13937–13944.

  • Rodriquez-Fernandez JL, Geiger B, Salomon D and Ben-Ze'ev A . (1993). J. Cell Biol., 122, 1285–1294.

  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S and Polakis P . (1996). Science, 272, 1023–1026.

  • Safer D, Elzinga M and Nachmias VT . (1991). J. Biol. Chem., 266, 4029–4032.

  • Safer D, Golla R and Nachmias VT . (1990). Proc. Natl. Acad. Sci. USA, 87, 2536–2540.

  • Sanger JM, Golla R, Safer D, Choi JK, Yu KR, Sanger JW and Nachmias VT (1995). Cell Motil. Cytoskel., 31, 307–322.

  • Santelli G, Califano D, Chiappetta G, Vento MT, Bartoli PC, Zullo F, Trapasso F, Viglietto G and Fusco A . (1999). Am. J. Pathol., 155, 799–804.

  • Sardi I and Tintori V . (2002). Int. J. Mol. Med., 9, 541–545.

  • Schreiber E, Matthias P, Muller M and Schaffner W . (1989). Nucleic Acids Res., 17, 6419.

  • Sellin JH, Umar S, Xiao J and Morris AP . (2001). Cancer Res., 61, 1899–1906.

  • Sosne G, Hafeez S, Greenberry II AL and Kurpakus-Wheater M . (2002). Curr. Eye Res., 24, 268–273.

  • Su Y, Chang SL and Hsiao HL . (2000). Mol. Cell. Biochem., 203, 163–167.

  • Sun HQ, Kwiatkowska K and Yin HL . (1996). J. Biol. Chem., 271, 9223–9230.

  • Takeichi M . (1991). Science, 251, 1451–1455.

  • Takeichi M . (1995). Curr. Opin. Cell Biol., 7, 619–627.

  • Tang RY and Su Y . (1997). J. Virol. Methods, 65, 153–158.

  • Tetsu O and McCormick F . (1999). Nature, 398, 422–426.

  • Varnum-Finney B and Reichardt LF . (1994). J. Cell Biol., 127, 1071–1084.

  • Verghese-Nikolakaki S, Apostolikas N, Livaniou E, Ithakissios DS and Evangelatos GP . (1996). Br. J. Cancer, 74, 1441–1444.

  • Vogelstein B and Kinzler KW . (1993). Trends Genet., 9, 138–141.

  • Weterman MA, van-Muijen GN, Ruiter DJ and Bloemers HP . (1993). Int. J. Cancer, 53, 278–284.

  • Xie D, Jauch A, Miller CW, Bartram CR and Koeffler HP . (2002). Int. J. Oncol., 21, 499–507.

  • Yamamoto T, Gotoh M, Kitajima M and Hirohashi S . (1993). Biochem. Biophys. Res. Commun., 193, 706–710.

  • Yu FX, Lin SC, Morrison-Bogorad M, Atkinson MAL and Yin HL . (1994). Cell Motil. Cytoskel., 27, 13–25.

Download references

Acknowledgements

This study was supported in part by Grants NSC 89-2320-B-010-126 and NSC 90-2314-B-075-080 from the Nation Science Council and in part by the Grant 89-B-FA22-2-4 (Program for Promoting Academic Excellence of Universities) of the Republic of China.

Author information

Authors and Affiliations

  1. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China

    Wei-Shu Wang

  2. Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    Wei-Shu Wang & Po-Min Chen

  3. Institute of Pharmacology, College of Life Science, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China

    Hung-Liang Hsiao

  4. Institute of Biopharmaceutical Science, College of Life Science, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China

    Sy-Yeuan Ju & Yeu Su

Authors
  1. Wei-Shu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Po-Min Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hung-Liang Hsiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sy-Yeuan Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yeu Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yeu Su.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, WS., Chen, PM., Hsiao, HL. et al. Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells. Oncogene 22, 3297–3306 (2003). https://doi.org/10.1038/sj.onc.1206404

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206404

Keywords

This article is cited by

Search

Advanced search

Quick links