Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell - PubMed (original) (raw)

Kenji Tsuchihashi, Takatsugu Ishimoto, Takeshi Motohara, Momoko Yoshikawa, Go J Yoshida, Takeyuki Wada, Takashi Masuko, Kaoru Mogushi, Hiroshi Tanaka, Tsuyoshi Osawa, Yasuharu Kanki, Takashi Minami, Hiroyuki Aburatani, Mitsuyo Ohmura, Akiko Kubo, Makoto Suematsu, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano

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Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell

Toshifumi Yae et al. Nat Commun. 2012.

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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.

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References

    1. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63 - PubMed
    1. J Cell Mol Med. 2009 Aug;13(8B):2236-2252 - PubMed
    1. J Exp Med. 1997 Dec 15;186(12):1985-96 - PubMed
    1. Cell. 1991 Apr 5;65(1):13-24 - PubMed
    1. Cancer Res. 1995 Oct 1;55(19):4297-301 - PubMed

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