AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas

·发布 2015年4月12日 ·更新 2015年8月19日

样本数

实验数

实验描述

Phosphoinositide-3-kinase (PI3K)-α inhibitors are clinically active in squamous carcinoma (SCC) of the head and neck (H&N) bearing mutations or amplification of PIK3CA. We aimed to identify potential mechanism of resistance and have observed that SCCs cells overcome the antitumor effects of the PI3Kα inhibitor BYL719 by maintaining PI3K-independent activation of the mammalian target of rapamycin (mTOR). The persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. We found that AXL is overexpressed in resistant tumors, dimerizes with the epidermal growth factor receptor (EGFR), phosphorylates EGFR tyrosine 1173, resulting in activation of phospholipase Cγ (PLCγ)- protein kinase C (PKC) that, in turn, activates mTOR. Finally, simultaneous treatment with PI3Kα and either EGFR, AXL or PKC inhibitors reverts this resistance. RNAseq from acquired resistant cells CAL33B, K180B were compared to their parental counterpart CAL33 and K180, respectively. K180 is a shortcut of KYSE180, and B stands for BYL719. Duplicate of parental sensitive cells and K180B, and triplicate for CAL33B.

样本属性

organism

Homo sapiens

resistant

No, Yes

实验信息

登记号

E-GEOD-61515

GEO 编号

SRP047251, GSE61515

实验类型

RNA-seq of coding RNA

物种

Homo sapiens

发布日期

2015年4月12日

更新日期

2015年8月19日

提交者

Maurizio Scaltriti、 Rita Das、 Trever G Bivona、 Ana O Benzaken、 Darcy A Kerr、 Qing Sheng、 Joseph M Gurski、 Jordi Rodon、 Raphael A Pelossof、 Manway Liu、 Jenny J Yan、 Angela Tam、 Yan Chen、 Huiqin Wang、 Alan Huang、 Jinsheng Liang、 Samuel Brook、 José Baselga、 Evangelos Pazarentzos、 Ronald A Ghissein、 Natasha Morse、 Neal Rosen、 Nicholas D Socci、 Dejan Juric、 Cristina Teixidó、 Rafael Rosell、 Moshe Elkabets

外部链接

ArrayExpress 原始页 NCBI GEO：SRP047251, GSE61515

分析服务

AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas

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