CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression.
CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression.
复制标题
DOI：
10.1016/j.oraloncology.2012.11.009
复制
发表时间：
2013-04
期刊：
影响因子：
4.8
通讯作者：
Franzmann, Elizabeth J.
中科院分区：
文献类型：
--
作者：
Perez, Aymee;Neskey, David M.;Wen, Judy;Pereira, Lutecia;Reategui, Erika P.;Goodwin, W. Jarrard;Carraway, Kermit L.;Franzmann, Elizabeth J.
关键词：
CD44是头颈部鳞状细胞癌（HNSCC）治疗的一个有前途的靶点，在肿瘤发生中有两个明确的作用：它是癌症干细胞（CSC）标志物，通过与许多信号分子相互作用促进迁移和增殖。本研究旨在探讨CD44在HNSCC癌变过程中的作用。通过在HNSCC细胞中过表达CD44，研究其对细胞增殖、迁移、凋亡及顺铂耐药的影响。我们还通过siRNA方法、免疫组织化学（IHC）和蛋白质印迹分析评估了CD44对肿瘤进展的影响。激光共聚焦显微镜观察CAL 27细胞中CD44和EGFR共定位。免疫沉淀法分析CD44与EGFR的相互作用。过表达CD44可增强SCC 25细胞的增殖和迁移，并与顺铂耐药性增加和细胞凋亡抑制相关。下调CAL 27细胞中的CD44可抑制组成性EGFR磷酸化，并显著降低裸鼠中的肿瘤生长。CD44和EGFR共定位于CAL 27细胞中。在CAL 27细胞中，CD44与EGFR共免疫沉淀，表明这些蛋白质相互作用。HNSCC中的CD44治疗可以靶向CSC群体并改变EGFR信号传导。
CD44 is a promising target for therapy in Head and Neck Squamous Cell carcinoma (HNSCC) and has two defined roles in tumorigenesis: it is a cancer stem cell (CSC) marker and it promotes migration and proliferation through interaction with many signaling molecules. The purpose of this study was to investigate the role of CD44 in HNSCC carcinogenesis. The effects of CD44 in cell proliferation, migration, apoptosis and cisplatin resistance were studied by its overexpression in HNSCC cells. We also evaluated the effect of CD44 on tumor progression by siRNA methodology, immunohistochemistry (IHC) and western blot analysis. CD44 and EGFR colocalization were examined in CAL 27 cells by laser scanning confocal microscopy. The interaction between CD44 and EGFR was analyzed by immunoprecipation. Overexpression of CD44 enhances cell proliferation and migration and correlates with increased cisplatin resistance and apoptosis inhibition in SCC25 cells. Downregulation of CD44 in CAL27 cells inhibited constitutive EGFR phosphorylation and significantly reduced tumor growth in nude mice. CD44 and EGFR colocalized in CAL 27 cells. CD44 coimmunoprecipated with EGFR in CAL 27 cells, indicating that these proteins interact with each other. CD44 therapy in HNSCC may target the CSC population and alter EGFR signaling.
登录
查看更多内容
DOI：
10.1083/jcb.128.4.673
发表时间：
1995-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jackson DG;Bell JI;Dickinson R;Timans J;Shields J;Whittle N
通讯作者：
Whittle N
影响因子：
3.1
作者：
Pereira, Lutecia H. Mateus;Adebisi, Islamiyat Nancy;Franzmann, Elizabeth J.
通讯作者：
Franzmann, Elizabeth J.
影响因子：
3.5
作者：
Hirvikoski, P;Tammi, R;Kosma, VM
通讯作者：
Kosma, VM
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK