Journal Article

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

Hannon, Gregory J., Yuan, Xin, Lupien, Mathieu, Heng, Yujing J., Kamel, Yahia M., Kron, Ken J., Kislinger, Thomas, Robert-Tissot, Celine, Sonzogni, Olmo, Seifried, Laurie A., Yeung, Faith Au, Wulf, Gerbug M., Wagenblast, Elvin, BeGora, Michael D., Haynes, Jennifer, Huang, Kai, Muthuswamy, Senthil K.

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Biology / Biology and Life Sciences / Biophysics / Breast cancer / Cancer / Cell culture / Cell Division - genetics / Cell Line, Tumor / Cell Movement - genetics / Cell survival / Epithelial cells / Epithelial Cells - pathology / Female / Fluorescence / Gene sequencing / Genes / Genes, Reporter - genetics / Green Fluorescent Proteins - genetics / Health aspects / Health care networks / Invasiveness / Keratin / Keratin-14 - genetics / Keratin-8 - genetics / Laboratories / Mammary gland / Mammary Glands, Animal - cytology / Mammary Glands, Animal - pathology / Mammary Neoplasms, Animal - genetics / Mammary Neoplasms, Animal - pathology / Medical prognosis / Medical research / Medical schools / Medicine / Medicine and Health Sciences / Membrane Proteins - genetics / Membrane Proteins - metabolism / Metastases / Metastasis / Methods and Resources / Mice / Mice, Inbred BALB C / Mice, Transgenic / Neoplasm Metastasis - pathology / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - metabolism / p53 Protein / Pathology / Promoter Regions, Genetic - genetics / Proteins / Publishing / Research and Analysis Methods / Ribonucleic acid / RNA / Secretome / Suicide / Suicide genes / Survival analysis / Toxins / Transgenic mice / Tumors