Abstract:
:In cancer metastasis, various environmental stressors attack the disseminating cells. The successful colonization of cancer cells in secondary sites therefore requires the ability of the cells to avoid the consequences of such exposure to the stressors. Here we show that orthotopic transplantation of a CD44 variant isoform-expressing (CD44v(+)) subpopulation of 4T1 breast cancer cells, but not that of a CD44v(-) subpopulation, in mice results in efficient lung metastasis accompanied by expansion of stem-like cancer cells. Such metastasis is dependent on the activity of the cystine transporter xCT, and the stability of this protein is controlled by CD44v. We find that epithelial splicing regulatory protein 1 regulates the expression of CD44v, and knockdown of epithelial splicing regulatory protein 1 in CD44v(+) cells results in an isoform switch from CD44v to CD44 standard (CD44s), leading to reduced cell surface expression of xCT and suppression of lung colonization. The epithelial splicing regulatory protein 1-CD44v-xCT axis is thus a potential therapeutic target for the prevention of metastasis.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Yae T,Tsuchihashi K,Ishimoto T,Motohara T,Yoshikawa M,Yoshida GJ,Wada T,Masuko T,Mogushi K,Tanaka H,Osawa T,Kanki Y,Minami T,Aburatani H,Ohmura M,Kubo A,Suematsu M,Takahashi K,Saya H,Nagano Odoi
10.1038/ncomms1892subject
Has Abstractpub_date
2012-06-06 00:00:00pages
883issn
2041-1723pii
ncomms1892journal_volume
3pub_type
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