Phosphorylation of LIFR promotes prostate cancer progression by activating the AKT pathway. (1st June 2019)

• Record Type: Journal Article
• Authors: Shao, Jialiang; Zhu, Wencheng; Ding, Yufeng; Zhu, Hongwen; Jing, Xiaoqian; Yu, Hua; Lu, Mujun; Qiao, Yunbo; Wang, Xiang; Ai, Hua; Wang, Xiongjun
• Is Part Of: Cancer letters. Volume 451(2019)
• Page Start: 110
• Page End: 121
• Publication Date: 2019-06-01
• Subjects: LIFR -- Phosphorylation -- Prostate cancer -- AKT; PCa prostate cancer -- LIFR leukemia inhibitory factor receptor -- JAK Janus protein tyrosine kinase -- STAT signal transducer and activator of transcription -- MAPK mitogen-activated protein kinase -- PI3K phosphoinositol 3-kinase -- CCK-8 Cell Counting Kit-8 -- LC-MS/MS liquid chromatography coupled with tandem mass spectrometry -- shRNA short hairpin RNA -- BLI bioluminescence imaging; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.02.042
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: LIFR plays an oncogenic role in PCa. Compared to normal prostate tissues, phosphorylation of serine 1044 in LIFR is significantly elevated in PCa. LIFR p-S1044 activates AKT pathway to promote PCa growth and metastasis. LIFR p-S1044 is a potential therapeutic target and a diagnostic biomarker of PCa.