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.
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
Cancer Lett. 2019 Jun 1;451:110-121. doi: 10.1016/j.canlet.2019.02.042. Epub 2019 Mar 6.
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.
前列腺癌（PCa）是男性中最常见的实体器官恶性肿瘤，其发病人数超过肺癌和结直肠癌，且由于高转移性，它是美国男性肿瘤相关死亡的第二大主要原因。最近，白血病抑制因子受体（LIFR）已被发现于多种癌症中发挥作用。然而，LIFR 在 PCa 进展中的作用仍有待揭示。在这项研究中，我们发现 LIFR 在 PCa 中发挥致癌作用。LIFR 的 S1044 磷酸化有助于随后 AKT 通路的激活，诱导一系列增殖和转移基因的表达。此外，LIFR-S1044 由 ERK2 而不是 ERK1 磷酸化。PCa 组织中 pLIFR-S1044 和 pAKT S473 的信号强度显示出紧密的正相关。ERK2/LIFR/AKT 轴调节 PCa 的进展，为 PCa 提供了有前途的治疗和诊断靶点。
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