Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Requirement for Arf6 in Breast Cancer Invasive Activities

Shigeru Hashimoto, Yasuhito Onodera, Ari Hashimoto, Miwa Tanaka, Michinari Hamaguchi, Atsuko Yamada, Hisataka Sabe and Hidesaburo Hanafusa
Proceedings of the National Academy of Sciences of the United States of America
Vol. 101, No. 17 (Apr. 27, 2004), pp. 6647-6652
Stable URL: http://www.jstor.org/stable/3372137
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Requirement for Arf6 in Breast Cancer Invasive Activities
Preview not available

Abstract

In most human breast cancer cell lines, there is a direct correlation between their in vivo invasive phenotypes and in vitro invasion activities. Here, we found that ADP-ribosylation factor 6 (Arf6) is localized at the invadopodia of the cultured breast cancer cells MDA-MB-231, and its suppression by a small-interfering RNA duplex effectively blocks the invasive activities of the cells, such as invadopodia formation, localized matrix degradation and Matrigel transmigration but not the cell-adhesion activity. We also found that the GTP hydrolysis-defective mutant Arf6(Q67L) and the GTP-binding defective mutant Arf6(T27N) both blocked these invasive activities but not cell adhesion, suggesting the necessity of continued activation and cycling of the Arf6 GTPase cycle in invasion. Among the different human breast cancer cell lines that we examined, cell lines with high invasive activities expressed higher amounts of Arf6 protein than those in weakly invasive and noninvasive cell lines, although no notable correlation was found between Arf6 mRNA expression levels and invasive activities. Moreover, Matrigel-transmigration activity of all of these invasive cells was blocked effectively by an Arf6 small-interfering RNA duplex. Hence, Arf6 appears to be an integral component of breast cancer invasive activities, and we propose that Arf6 and the intracellular machinery regulating Arf6 during invasion should be considered as therapeutic targets for the prevention of breast cancer invasion.

Page Thumbnails

  • Thumbnail: Page 
[6647]
    [6647]
  • Thumbnail: Page 
6648
    6648
  • Thumbnail: Page 
6649
    6649
  • Thumbnail: Page 
6650
    6650
  • Thumbnail: Page 
6651
    6651
  • Thumbnail: Page 
6652
    6652