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论文题目: A CD44v(+) subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity
英文论文题目: A CD44v(+) subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity
第一作者: Hu, J; Li, G; Zhang, PY; Zhuang, XQ; Hu, GH
英文第一作者: Hu, J; Li, G; Zhang, PY; Zhuang, XQ; Hu, GH
联系作者: Hu, GH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, 320 Yueyang Rd, Beijing 100864, Peoples R China.
英文联系作者: Hu, GH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, 320 Yueyang Rd, Beijing 100864, Peoples R China.
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发表年度: 2017
卷: 8
期:
页码: e2679
摘要: Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24(-)/CD44(+) breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness. Directly suppressing CD44v expression significantly alleviates the metastasis burden in lungs. Mechanically, CD44v, but not CD44s, responds to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis. In clinical samples expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis. Overall, our data identify a subset of metastatic breast CSCs characterized by CD44v expression, and suggest that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.
英文摘要: Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24(-)/CD44(+) breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness. Directly suppressing CD44v expression significantly alleviates the metastasis burden in lungs. Mechanically, CD44v, but not CD44s, responds to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis. In clinical samples expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis. Overall, our data identify a subset of metastatic breast CSCs characterized by CD44v expression, and suggest that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.
刊物名称: CELL DEATH & DISEASE
英文刊物名称: CELL DEATH & DISEASE
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 5.965
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论文类别: Article
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