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Status |
Public on May 06, 2019 |
Title |
Characterization of the ALK7 signaling pathway in PanNET, using cell lines that either express dominant negative ALK7 (ALK7-DN), or subjected to ALK7 knock-down (shALK7), treated with activin B |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Herein we report that the TGFß superfamily receptor ALK7 is a suppressor of tumorigenesis and metastasis, as revealed by functional studies in mouse models of pancreatic neuroendocrine and luminal breast cancer, complemented by experimental metastasis assays. Activation in neoplastic cells of the ALK7 signaling pathway by its principal ligand activin B induces apoptosis. During tumorigenesis, cancer cells use two different approaches to evade this barrier, either downregulating activin B and/or ALK7. Suppressing ALK7 expression additionally contributes to the capability for metastatic seeding. ALK7 is associated with shorter relapse-free survival of various human cancers and distant-metastasis-free survival of breast cancer patients. This study introduces a new mechanistic insight into primary and metastatic tumor development, in the form of a protective barrier that triggers apoptosis in cells that are not ‘authorized’ to proliferate within a particular tissue, by virtue of those cells expressing ALK7 in a tissue microenvironment bathed in its ligand.
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Overall design |
We performed RNA-seq after treatment with activin B of control ßTC3 cells, ßTC3 cells with DOX-inducible expression of either wild type ALK7 or ALK7-DN, and ßTC3 cells with DOX-inducible ALK7 knock-down.
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Contributor(s) |
Michael I, Zangger N, Hanahan D |
Citation(s) |
31063757 |
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Submission date |
Sep 13, 2017 |
Last update date |
May 08, 2019 |
Contact name |
Nadine Fournier |
E-mail(s) |
nadine.fournier@sib.swiss
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Organization name |
Agora Cancer Research Center & Swiss Institute of Bioinformatics
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Lab |
Translational Data Science Facility
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Street address |
Agora Cancer Research Center, Bugon 25A
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City |
Lausanne |
State/province |
Vaud |
ZIP/Postal code |
1000 |
Country |
Switzerland |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (30)
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This SubSeries is part of SuperSeries: |
GSE103800 |
ALK7 signaling manifests a homeostatic tissue barrier necessarily abrogated during tumorigenesis and metastasis |
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Relations |
BioProject |
PRJNA407261 |
SRA |
SRP117681 |