ALK7 Signaling Manifests a Homeostatic Tissue Barrier That Is Abrogated during Tumorigenesis and Metastasis.

Michael, Iacovos P; Saghafinia, Sadegh; Tichet, Mélanie; Zangger, Nadine; Marinoni, Ilaria; Perren, Aurel; Hanahan, Douglas (2019). ALK7 Signaling Manifests a Homeostatic Tissue Barrier That Is Abrogated during Tumorigenesis and Metastasis. Developmental cell, 49(3), 409-424.e6. Cell Press 10.1016/j.devcel.2019.04.015

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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 downregulating 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 mechanistic insights 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Marinoni, Ilaria and Perren, Aurel

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1534-5807

Publisher:

Cell Press

Language:

English

Submitter:

Aurel Perren

Date Deposited:

13 Nov 2019 16:53

Last Modified:

13 Nov 2019 16:58

Publisher DOI:

10.1016/j.devcel.2019.04.015

PubMed ID:

31063757

Uncontrolled Keywords:

ALK7/Acvr1c PanNETs TGFß superfamily activin B breast cancer endothelial cells metastasis neuroendocrine tumors

BORIS DOI:

10.7892/boris.134736

URI:

https://boris.unibe.ch/id/eprint/134736

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