Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne 1015, Switzerland.
Bioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne 1015, Switzerland.
Dev Cell. 2019 May 6;49(3):409-424.e6. doi: 10.1016/j.devcel.2019.04.015.
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.
在这里，我们报告 TGFß 超家族受体 ALK7 是肿瘤发生和转移的抑制剂，这是通过在胰腺神经内分泌和腔乳腺癌的小鼠模型中的功能研究揭示的，辅以实验转移测定。其主要配体激活素 B 在肿瘤细胞中激活 ALK7 信号通路会诱导细胞凋亡。在肿瘤发生过程中，癌细胞使用两种不同的方法来逃避这种障碍，要么下调激活素 B，要么下调 ALK7。抑制 ALK7 的表达还会增加转移播种的能力。ALK7 与各种人类癌症的无复发生存期和乳腺癌患者的无远处转移生存期较短有关。这项研究通过一种保护屏障为原发性和转移性肿瘤的发展提供了机制上的见解，该屏障通过表达 ALK7 的组织微环境中的配体触发那些在特定组织中未被“授权”增殖的细胞凋亡。
