Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo.
The contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-06-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004049&type=printable |
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| author | Olmo Sonzogni Jennifer Haynes Laurie A Seifried Yahia M Kamel Kai Huang Michael D BeGora Faith Au Yeung Celine Robert-Tissot Yujing J Heng Xin Yuan Gerbug M Wulf Ken J Kron Elvin Wagenblast Mathieu Lupien Thomas Kislinger Gregory J Hannon Senthil K Muthuswamy |
| author_facet | Olmo Sonzogni Jennifer Haynes Laurie A Seifried Yahia M Kamel Kai Huang Michael D BeGora Faith Au Yeung Celine Robert-Tissot Yujing J Heng Xin Yuan Gerbug M Wulf Ken J Kron Elvin Wagenblast Mathieu Lupien Thomas Kislinger Gregory J Hannon Senthil K Muthuswamy |
| author_sort | Olmo Sonzogni |
| collection | DOAJ |
| description | The contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice express the reporter genes in the right cell compartments of mammary gland epithelia and respond to treatment with toxins. In addition, we engineered the reporters into 4T1 metastatic mouse tumor cell line and demonstrate that K14+ cells, but not K14- or K8+, are both highly invasive in three-dimensional (3D) culture and metastatic in vivo. Treatment of cells in culture, or tumors in mice, with reporter-targeting toxin inhibited both invasive behavior and metastasis in vivo. RNA sequencing (RNA-seq), secretome, and epigenome analysis of K14+ and K14- cells led to the identification of amphoterin-induced protein 2 (Amigo2) as a new cell invasion driver whose expression correlated with decreased relapse-free survival in patients with TP53 wild-type (WT) breast cancer. |
| format | Article |
| id | doaj-art-5f14a8b0f9b94d6189d917aeaebfeb35 |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2018-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-5f14a8b0f9b94d6189d917aeaebfeb352025-08-20T03:11:25ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852018-06-01166e200404910.1371/journal.pbio.2004049Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo.Olmo SonzogniJennifer HaynesLaurie A SeifriedYahia M KamelKai HuangMichael D BeGoraFaith Au YeungCeline Robert-TissotYujing J HengXin YuanGerbug M WulfKen J KronElvin WagenblastMathieu LupienThomas KislingerGregory J HannonSenthil K MuthuswamyThe contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice express the reporter genes in the right cell compartments of mammary gland epithelia and respond to treatment with toxins. In addition, we engineered the reporters into 4T1 metastatic mouse tumor cell line and demonstrate that K14+ cells, but not K14- or K8+, are both highly invasive in three-dimensional (3D) culture and metastatic in vivo. Treatment of cells in culture, or tumors in mice, with reporter-targeting toxin inhibited both invasive behavior and metastasis in vivo. RNA sequencing (RNA-seq), secretome, and epigenome analysis of K14+ and K14- cells led to the identification of amphoterin-induced protein 2 (Amigo2) as a new cell invasion driver whose expression correlated with decreased relapse-free survival in patients with TP53 wild-type (WT) breast cancer.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004049&type=printable |
| spellingShingle | Olmo Sonzogni Jennifer Haynes Laurie A Seifried Yahia M Kamel Kai Huang Michael D BeGora Faith Au Yeung Celine Robert-Tissot Yujing J Heng Xin Yuan Gerbug M Wulf Ken J Kron Elvin Wagenblast Mathieu Lupien Thomas Kislinger Gregory J Hannon Senthil K Muthuswamy Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. PLoS Biology |
| title | Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. |
| title_full | Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. |
| title_fullStr | Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. |
| title_full_unstemmed | Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. |
| title_short | Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. |
| title_sort | reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004049&type=printable |
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