Phosphorylation of LIFR promotes prostate cancer progression by activating the AKT pathway

Jialiang Shao; Wencheng Zhu; Yufeng Ding; Hongwen Zhu; Xiaoqian Jing; Hua Yu; Mujun Lu; Yunbo Qiao; Xiang Wang; Hua Ai; Xiongjun Wang

doi:10.1016/j.canlet.2019.02.042

Phosphorylation of LIFR promotes prostate cancer progression by activating the AKT pathway

Cancer Lett. 2019 Jun 1:451:110-121. doi: 10.1016/j.canlet.2019.02.042. Epub 2019 Mar 6.

Authors

Jialiang Shao¹, Wencheng Zhu², Yufeng Ding³, Hongwen Zhu⁴, Xiaoqian Jing⁵, Hua Yu⁶, Mujun Lu³, Yunbo Qiao⁷, Xiang Wang⁸, Hua Ai⁹, Xiongjun Wang¹⁰

Affiliations

¹ Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China; Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 200080, China.
² Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
³ Department of Urology and Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.
⁴ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: zhw@simm.ac.cn.
⁵ Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
⁶ Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China.
⁷ Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China. Electronic address: ybqiao@gzhu.edu.cn.
⁸ Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 200080, China. Electronic address: drseanwang@163.com.
⁹ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610065, China.
¹⁰ Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China. Electronic address: xjwang02@sibcb.ac.cn.

PMID: 30851421
DOI: 10.1016/j.canlet.2019.02.042

Abstract

Prostate cancer (PCa) is the most common solid organ malignancy among men, outnumbering both lung and colorectal cancer, and it is the second leading cause of male tumor-related death in the United States due to high metastasis. Recently, leukemia inhibitory factor receptor (LIFR) has been found to play roles in multiple types of cancer. However, the roles of LIFR in the progression of PCa remain to be revealed. In this study, we found that LIFR plays an oncogenic role in PCa. The phosphorylation of LIFR at S1044 contributes to subsequent activation of the AKT pathway, inducing the expression of a series of proliferation and metastatic genes. Additionally, LIFR-S1044 is phosphorylated by ERK2 but not ERK1. The signal intensity of pLIFR-S1044 and pAKT S473 in PCa tissue displays a tight positive correlation. The ERK2/LIFR/AKT axis modulates PCa progression and offers a promising therapeutic and diagnostic target for PCa.

Keywords: AKT; LIFR; Phosphorylation; Prostate cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Heterografts
Humans
Leukemia Inhibitory Factor Receptor alpha Subunit / metabolism*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Phosphorylation
Prostatic Neoplasms / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*

Substances

LIFR protein, human
Leukemia Inhibitory Factor Receptor alpha Subunit
Proto-Oncogene Proteins c-akt