气体6
AXL受体酪氨酸激酶
癌症研究
转移
医学
癌症
受体酪氨酸激酶
三阴性乳腺癌
生物
癌细胞
内科学
酪氨酸激酶
乳腺癌
抗体
肿瘤科
免疫疗法
血管生成
肿瘤微环境
贝伐单抗
免疫组织化学
化疗
信号转导
细胞生物学
JAK-STAT信号通路
遗传学
作者
Wilhem Leconet,Myriam Chentouf,Stanislas du Manoir,Clément Chevalier,Audrey Sirvent,Imade Aït-Arsa,Muriel Busson,Marta Jarlier,Nina Radosevic‐Robin,Charles Theillet,Dany Chalbos,Jean‐Max Pasquet,André Pèlegrin,Christel Larbouret,Bruno Robert
标识
DOI:10.1158/1078-0432.ccr-16-1316
摘要
Abstract Purpose: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC). Experimental Design: We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration, and invasion signaling pathways. Results: Treatment with 20G7-D9 inhibited tumor growth and bone metastasis formation in AXL-positive TNBC cell xenografts or PDX, but not in AXL-negative PDX, highlighting AXL role in cancer growth and invasion. In vitro stimulation of AXL-positive cancer cells by its ligand GAS6 induced the expression of several EMT-associated genes (SNAIL, SLUG, and VIM) through an intracellular signaling implicating the transcription factor FRA-1, important in cell invasion and plasticity, and increased their migration/invasion capacity. 20G7-D9 induced AXL degradation and inhibited all AXL/GAS6–dependent cell signaling implicated in EMT and in cell migration/invasion. Conclusions: The anti-AXL antibody 20G7-D9 represents a promising therapeutic strategy in TNBC with mesenchymal features by inhibiting AXL-dependent EMT, tumor growth, and metastasis formation. Clin Cancer Res; 23(11); 2806–16. ©2016 AACR.
科研通智能强力驱动
Strongly Powered by AbleSci AI