Abstract:
: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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Block I,Müller C,Sdogati D,Pedersen H,List M,Jaskot AM,Syse SD,Lund Hansen P,Schmidt S,Christiansen H,Casella C,Bering Olsen S,Blomstrøm MM,Riedel A,Thomassen M,Kruse TA,Karlskov Hansen SW,Kioschis P,Mollenhauer Jdoi
10.1038/s41388-019-0739-0subject
Has Abstractpub_date
2019-06-01 00:00:00pages
4560-4573issue
23eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0739-0journal_volume
38pub_type
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