Journal Article

CFP suppresses breast cancer cell growth by TES-mediated upregulation of the transcription factor DDIT3

Riedel, Angela, Jaskot, Aleksandra M., Müller, Carolin, Pedersen, Henriette, Bering Olsen, Sidsel, Kioschis, Petra, List, Markus, Lund Hansen, Pernille, Karlskov Hansen, Søren W., Blomstrøm, Monica M., Kruse, Torben A., Schmidt, Steffen, Casella, Cinzia, Christiansen, Helle, Mollenhauer, Jan, Block, Ines, Syse, Silje Damkjær, Sdogati, Daniel, Thomassen, Mads

2019

Overview

Breast cancer is a heterogeneous genetic disease driven by the accumulation of individual mutations per tumor. Whole-genome sequencing approaches have identified numerous genes with recurrent mutations in primary tumors. Although mutations in well characterized tumor suppressors and oncogenes are overrepresented in these sets, the majority of the genetically altered genes have so far unknown roles in breast cancer progression. To improve the basic understanding of the complex disease breast cancer and to potentially identify novel drug targets or regulators of known cancer-driving pathways, we analyzed 86 wild-type genes and 94 mutated variants for their effect on cell growth using a serially constructed panel of MCF7 cell lines. We demonstrate in subsequent experiments that the metal cation transporter CNNM4 regulates growth by induction of apoptosis and identified a tumor suppressive role of complement factor properdin (CFP) in vitro and in vivo. CFP appears to induce the intracellular upregulation of the pro-apoptotic transcription factor DDIT3 which is associated with endoplasmic reticulum-stress response.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/109 / 13/2 / 13/31 / 13/89 / 38 / 38/61 / 38/77 / 631/67/1347 / 631/80/304 / 64/60 / Animals / Apoptosis / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Cations / Cell Biology / Cell growth / Cell Proliferation - drug effects / Cell Survival / Cellular stress response / Cytoskeletal Proteins - metabolism / Development and progression / Diagnosis / Disease Progression / DNA sequencing / Endoplasmic reticulum / Endoplasmic Reticulum - metabolism / Endoplasmic Reticulum Stress - drug effects / Female / Gene Expression Profiling / Genetic aspects / Genetic transcription / Genomes / Human Genetics / Humans / Internal Medicine / LIM Domain Proteins - metabolism / MCF-7 Cells / Medicine / Medicine & Public Health / Metal ions / Mice / Mice, Inbred NOD / Mice, SCID / Mutation / Neoplasm Transplantation / Nucleotide sequencing / Oncology / Patient outcomes / Phenotype / Properdin / Properdin - metabolism / Sequence Analysis, DNA / Transcription Factor CHOP - metabolism / Transcription factors / Tumors / Up-Regulation / Whole genome sequencing