SKOR1 mediates FER kinase-dependent invasive growth of breast cancer cells

Author:

Sluimer Lilian,Bullock Esme,Rätze Max,Enserink Lotte,Overbeeke Celine,Hornsveld Marten,Brunton Valerie G.,Derksen Patrick W.B.ORCID,Tavares SandraORCID

Abstract

AbstractHigh expression of the tyrosine kinase FER is an independent prognostic factor that correlates with poor survival in breast cancer patients. To investigate whether the kinase activity is essential for FER oncogenic properties, we developed an ATP analogue-sensitive knock-in allele (FERASKI). Specific FER kinase inhibition in MDA-MD-231 cells reduces migration, invasion, and metastasis in a mouse model of breast cancer. Using the FERASKI system, we identify SKI family transcriptional corepressor 1 (SKOR1) as a direct FER kinase substrate. SKOR1 loss phenocopies FER inhibition, leading to impaired proliferation, migration and invasion, and inhibition of breast cancer growth and metastasis formation in mice. We show that the candidate FER phosphorylation residue, SKOR1-Y234, is essential for FER-dependent tumor progression features. Finally, our work suggests that the SKOR1-Y234 residue promotes Smad2/3 signaling through SKOR1 binding to Smad3 attenuation.Our study thus identifies SKOR1 as a mediator of FER-dependent breast cancer progression, advocating FER kinase inhibition as a candidate strategy to treat high-grade breast cancers.SummaryThe SKI FAMILY TRANSCRIPTIONAL COREPRESSOR 1 (SKOR1) has been mainly associated with neuronal development. Now, Sluimer et al. identify SKOR1 as a new substrate of the oncogenic tyrosine kinase FER, and a driver of TNBC progression.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3