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CD44 splice isoform switching determines breast cancer stem cell state.

Author(s): Zhang, Honghong; Brown, Rhonda L; Wei, Yong; Zhao, Pu; Liu, Sali; et al

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dc.contributor.authorZhang, Honghong-
dc.contributor.authorBrown, Rhonda L-
dc.contributor.authorWei, Yong-
dc.contributor.authorZhao, Pu-
dc.contributor.authorLiu, Sali-
dc.contributor.authorLiu, Xuan-
dc.contributor.authorDeng, Yu-
dc.contributor.authorHu, Xiaohui-
dc.contributor.authorZhang, Jing-
dc.contributor.authorGao, Xin D-
dc.contributor.authorKang, Yibin-
dc.contributor.authorMercurio, Arthur M-
dc.contributor.authorGoel, Hira Lal-
dc.contributor.authorCheng, Chonghui-
dc.date.accessioned2020-02-25T20:10:54Z-
dc.date.available2020-02-25T20:10:54Z-
dc.date.issued2019-02en_US
dc.identifier.citationZhang, Honghong, Brown, Rhonda L, Wei, Yong, Zhao, Pu, Liu, Sali, Liu, Xuan, Deng, Yu, Hu, Xiaohui, Zhang, Jing, Gao, Xin D, Kang, Yibin, Mercurio, Arthur M, Goel, Hira Lal, Cheng, Chonghui. (2019). CD44 splice isoform switching determines breast cancer stem cell state.. Genes & development, 33 (3-4), 166 - 179. doi:10.1101/gad.319889.118en_US
dc.identifier.issn0890-9369-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr18r2n-
dc.description.abstractAlthough changes in alternative splicing have been observed in cancer, their functional contributions still remain largely unclear. Here we report that splice isoforms of the cancer stem cell (CSC) marker CD44 exhibit strikingly opposite functions in breast cancer. Bioinformatic annotation in patient breast cancer in The Cancer Genome Atlas (TCGA) database reveals that the CD44 standard splice isoform (CD44s) positively associates with the CSC gene signatures, whereas the CD44 variant splice isoforms (CD44v) exhibit an inverse association. We show that CD44s is the predominant isoform expressed in breast CSCs. Elimination of the CD44s isoform impairs CSC traits. Conversely, manipulating the splicing regulator ESRP1 to shift alternative splicing from CD44v to CD44s leads to an induction of CSC properties. We further demonstrate that CD44s activates the PDGFRβ/Stat3 cascade to promote CSC traits. These results reveal CD44 isoform specificity in CSC and non-CSC states and suggest that alternative splicing provides functional gene versatility that is essential for distinct cancer cell states and thus cancer phenotypes.en_US
dc.format.extent1 - 15en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofGenes & developmenten_US
dc.rightsFinal published version. This is an open access article.en_US
dc.titleCD44 splice isoform switching determines breast cancer stem cell state.en_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1101/gad.319889.118-
dc.identifier.eissn1549-5477-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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