Plexin-B3表达刺激MET信号通路，乳腺癌干细胞分化和肺转移。
Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis.
发表日期：2023 Feb 28
作者：
Qiaozhu Zuo, Yongkang Yang, Yajing Lyu, Chen Yang, Chelsey Chen, Shaima Salman, Tina Yi-Ting Huang, Elizabeth E Wicks, Walter Jackson, Emmanuel Datan, Wenxin Qin, Gregg L Semenza
来源：
Stem Cell Research & Therapy
摘要：
肿瘤内缺氧是一种微环境特征，会促进乳腺癌的进展，并与癌症死亡率相关。Plexin B3（PLXNB3）在雌激素受体阴性乳腺癌中高度表达，但其潜在机制和后果尚未得到彻底研究。在这里，我们报告PLXNB3表达会随着缺氧而增加，并且在人类乳腺癌细胞中PLXNB3是缺氧诱导因子1（HIF-1）的直接靶基因。PLXNB3表达与HIF-1α免疫组织化学、乳腺癌分级和分期以及患者死亡率相关。机械上讲，PLXNB3对缺氧诱导的MET / SRC / 焦点性粘附激酶（FAK）和MET / SRC / STAT3 / NANOG信号传导以及缺氧诱导的乳腺癌细胞迁移、侵袭和癌症干细胞化有必要。PLXNB3沉默会影响正交移植乳腺癌小鼠模型的肿瘤形成和肺部转移。版权所有©2023年作者。Elsevier Inc.保留所有权利。
Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is associated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells. PLXNB3 expression is correlated with HIF-1α immunohistochemistry, breast cancer grade and stage, and patient mortality. Mechanistically, PLXNB3 is required for hypoxia-induced MET/SRC/focal adhesion kinase (FAK) and MET/SRC/STAT3/NANOG signaling as well as hypoxia-induced breast cancer cell migration, invasion, and cancer stem cell specification. PLXNB3 knockdown impairs tumor formation and lung metastasis in orthotopic breast cancer mouse models.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.