Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell
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 o...
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| Veröffentlicht in: | Nature communications 2012-06, Vol.3 (1), p.883-883, Article 883 |
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| creator | Yae, Toshifumi Tsuchihashi, Kenji Ishimoto, Takatsugu Motohara, Takeshi Yoshikawa, Momoko Yoshida, Go J. Wada, Takeyuki Masuko, Takashi Mogushi, Kaoru Tanaka, Hiroshi Osawa, Tsuyoshi Kanki, Yasuharu Minami, Takashi Aburatani, Hiroyuki Ohmura, Mitsuyo Kubo, Akiko Suematsu, Makoto Takahashi, Kazuhisa Saya, Hideyuki Nagano, Osamu |
| description | 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.
CD44 is a cell surface protein that is a marker for stem cell-like cancer cells and has a role in invasion and metastasis. Here, epithelial splicing regulatory protein 1 is shown to generate a CD44 variant protein that enhances metastasis in a mouse model and protects cells from oxidative stress. |
| doi_str_mv | 10.1038/ncomms1892 |
| format | Article |
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+
) 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.
CD44 is a cell surface protein that is a marker for stem cell-like cancer cells and has a role in invasion and metastasis. Here, epithelial splicing regulatory protein 1 is shown to generate a CD44 variant protein that enhances metastasis in a mouse model and protects cells from oxidative stress.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms1892</identifier><identifier>PMID: 22673910</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337/1645/1946 ; 631/67/1347 ; 631/67/322 ; 631/80/304 ; Alternative Splicing - genetics ; Animals ; Biology ; Breast cancer ; Breast Neoplasms - complications ; Breast Neoplasms - genetics ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Female ; Flow Cytometry ; Growth factors ; Humanities and Social Sciences ; Hyaluronan Receptors - genetics ; Immunoblotting ; Kinases ; Lung Neoplasms - genetics ; Lung Neoplasms - secondary ; Medical research ; Medicine ; Metastasis ; Mice ; Mice, Inbred BALB C ; multidisciplinary ; Proteins ; RNA, Messenger - genetics ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Science ; Science (multidisciplinary) ; Tumors</subject><ispartof>Nature communications, 2012-06, Vol.3 (1), p.883-883, Article 883</ispartof><rights>Springer Nature Limited 2012</rights><rights>Copyright Nature Publishing Group Jun 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-57e23d94ffc6595d2a5479e3b5345b8ee29b8bbf0b7e24ba9660c2b344535c153</citedby><cites>FETCH-LOGICAL-c494t-57e23d94ffc6595d2a5479e3b5345b8ee29b8bbf0b7e24ba9660c2b344535c153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncomms1892$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://doi.org/10.1038/ncomms1892$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41120,42189,51576</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/ncomms1892$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22673910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yae, Toshifumi</creatorcontrib><creatorcontrib>Tsuchihashi, Kenji</creatorcontrib><creatorcontrib>Ishimoto, Takatsugu</creatorcontrib><creatorcontrib>Motohara, Takeshi</creatorcontrib><creatorcontrib>Yoshikawa, Momoko</creatorcontrib><creatorcontrib>Yoshida, Go J.</creatorcontrib><creatorcontrib>Wada, Takeyuki</creatorcontrib><creatorcontrib>Masuko, Takashi</creatorcontrib><creatorcontrib>Mogushi, Kaoru</creatorcontrib><creatorcontrib>Tanaka, Hiroshi</creatorcontrib><creatorcontrib>Osawa, Tsuyoshi</creatorcontrib><creatorcontrib>Kanki, Yasuharu</creatorcontrib><creatorcontrib>Minami, Takashi</creatorcontrib><creatorcontrib>Aburatani, Hiroyuki</creatorcontrib><creatorcontrib>Ohmura, Mitsuyo</creatorcontrib><creatorcontrib>Kubo, Akiko</creatorcontrib><creatorcontrib>Suematsu, Makoto</creatorcontrib><creatorcontrib>Takahashi, Kazuhisa</creatorcontrib><creatorcontrib>Saya, Hideyuki</creatorcontrib><creatorcontrib>Nagano, Osamu</creatorcontrib><title>Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>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.
CD44 is a cell surface protein that is a marker for stem cell-like cancer cells and has a role in invasion and metastasis. Here, epithelial splicing regulatory protein 1 is shown to generate a CD44 variant protein that enhances metastasis in a mouse model and protects cells from oxidative stress.</description><subject>631/337/1645/1946</subject><subject>631/67/1347</subject><subject>631/67/322</subject><subject>631/80/304</subject><subject>Alternative Splicing - genetics</subject><subject>Animals</subject><subject>Biology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - complications</subject><subject>Breast Neoplasms - genetics</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Immunoprecipitation</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Growth factors</subject><subject>Humanities and Social Sciences</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Immunoblotting</subject><subject>Kinases</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - secondary</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>multidisciplinary</subject><subject>Proteins</subject><subject>RNA, Messenger - genetics</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Science</subject><subject>Science 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Osamu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2012-06-06</date><risdate>2012</risdate><volume>3</volume><issue>1</issue><spage>883</spage><epage>883</epage><pages>883-883</pages><artnum>883</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><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.
CD44 is a cell surface protein that is a marker for stem cell-like cancer cells and has a role in invasion and metastasis. Here, epithelial splicing regulatory protein 1 is shown to generate a CD44 variant protein that enhances metastasis in a mouse model and protects cells from oxidative stress.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22673910</pmid><doi>10.1038/ncomms1892</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/337/1645/1946 631/67/1347 631/67/322 631/80/304 Alternative Splicing - genetics Animals Biology Breast cancer Breast Neoplasms - complications Breast Neoplasms - genetics Cell Line, Tumor Chromatin Immunoprecipitation Female Flow Cytometry Growth factors Humanities and Social Sciences Hyaluronan Receptors - genetics Immunoblotting Kinases Lung Neoplasms - genetics Lung Neoplasms - secondary Medical research Medicine Metastasis Mice Mice, Inbred BALB C multidisciplinary Proteins RNA, Messenger - genetics RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Science Science (multidisciplinary) Tumors |
| title | Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell |
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