HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis

文献类型： 外文期刊

第一作者： Jiang, Qiwei

作者： Jiang, Qiwei;Zhang, Deyu;Liu, Juan;Liang, Chaoyang;Wu, Jun;Lin, Jing;Ye, Tianxing;Ding, Lihua;Li, Jianbin;Ye, Qinong;Jiang, Qiwei;Liu, Juan;Liang, Chaoyang;Yang, Ronghui;Li, Binghui;Zhang, Cheng;Wu, Jun;Lin, Jing;Gao, Shan

作者机构：

期刊名称：SCIENCE ADVANCES （ 影响因子：13.6； 五年影响因子：15.4 ）

ISSN： 2375-2548

年卷期： 2023 年 9 卷 23 期

页码：

收录情况： SCI

摘要： The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components. Experiments of HPIP knockout or knockdown and chemical inhibition of HPIP expression showed that HPIP is required for EGFR-RAS-ERK signaling complex formation, EGFR-RAS-ERK signaling activation, and EGFRRAS-ERK signaling-mediated promotion of aerobic glycolysis as well as cancer cell growth in vitro and in vivo. HPIP expression is correlated with EGFR-RAS-ERK signaling activation and predicts worse clinical outcomes in patients with lung cancer. These results provide insights into EGFR-RAS-ERK signaling complex formation and EGFR-RAS-ERK signaling regulation and suggest that HPIP may be a promising therapeutic target for cancer with dysregulated EGFR-RAS-ERK signaling.

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