美国斯坦福大学Michael F. Clarke小组的一项最新工作发现,LEFTY1是SMAD双重抑制因子,可促进乳祖细胞生长和肿瘤发生。相关论文于2020年7月20日在线发表在《细胞—干细胞》杂志上。
Title: LEFTY1 Is a Dual-SMAD Inhibitor that Promotes Mammary Progenitor Growth and Tumorigenesis
Author: Maider Zabala, Neethan A. Lobo, Jane Antony, Luuk S. Heitink, Gunsagar S. Gulati, Jessica Lam, Natesh Parashurama, Kassandra Sanchez, Maddalena Adorno, Shaheen S. Sikandar, Angera H. Kuo, Dalong Qian, Tomer Kalisky, Sopheak Sim, Linus Li, Frederick M. Dirbas, George Somlo, Aaron Newman, Stephen R. Quake, Michael F. Clarke
Issue&Volume: 2020-07-20
Abstract: SMAD pathways govern epithelial proliferation, and transforming growth factor β (TGF-βand BMP signaling through SMAD members has distinct effects on mammary developmentand homeostasis. Here, we show that LEFTY1, a secreted inhibitor of NODAL/SMAD2 signaling,is produced by mammary progenitor cells and, concomitantly, suppresses SMAD2 and SMAD5signaling to promote long-term proliferation of normal and malignant mammary epithelialcells. In contrast, BMP7, a NODAL antagonist with context-dependent functions, isproduced by basal cells and restrains progenitor cell proliferation. In normal mouseepithelium, LEFTY1 expression in a subset of luminal cells and rare basal cells opposesBMP7 to promote ductal branching. LEFTY1 binds BMPR2 to suppress BMP7-induced activationof SMAD5, and this LEFTY1-BMPR2 interaction is specific to tumor-initiating cellsin triple-negative breast cancer xenografts that rely on LEFTY1 for growth. Theseresults suggest that LEFTY1 is an endogenous dual-SMAD inhibitor and that suppressingits function may represent a therapeutic vulnerability in breast cancer.
DOI: 10.1016/j.stem.2020.06.017
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30284-8
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
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