Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo

Sonzogni, O., Haynes, J., Seifried, L. A., Kamel, Y. M., Huang, K., BeGora, M. D., Yeung, F. A., Robert-Tissot, C., Heng, Y. J., Yuan, X., Wulf, G. M., Kron, K. J., Wagenblast, E., Lupien, M., Kislinger, T., Hannon, G. J., Muthuswamy, S. K. (June 2018) Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo. PLoS Biol, 16 (6). e2004049. ISSN 1544-9173

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URL: https://www.ncbi.nlm.nih.gov/pubmed/29924804
DOI: 10.1371/journal.pbio.2004049

Abstract

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > metastasis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matthew Dunn
Date: 20 June 2018
Date Deposited: 23 Apr 2019 15:19
Last Modified: 23 Apr 2019 15:19
PMCID: PMC6042798
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37785

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