PIM1 kinase promotes cell proliferation, metastasis and tumor growth of lung adenocarcinoma by potentiating the c-MET signaling pathway
PIM1 kinase promotes cell proliferation, metastasis and tumor growth of lung adenocarcinoma by potentiating the c-MET signaling pathway
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DOI：
10.1016/j.canlet.2018.12.015
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Jiang, Richeng
中科院分区：
文献类型：
--
作者：
Cao, Lianjing;Wang, Fan;Jiang, Richeng
原癌基因PIM1在血液病和实体瘤的增殖、存活、转移和耐药中起重要作用。尽管PIM1已被证明与非小细胞肺癌的淋巴转移和预后不良有关，但其潜在的分子机制仍不清楚。在这里，我们发现PIM1在肺腺癌中经常过度表达，其表达水平与c-met的表达和不良的临床预后有关。我们进一步证明PIM1可能通过S406上真核细胞翻译起始因子4B(EIF4B)的磷酸化来调节c-met的表达。PIM1的缺失在体外减少了细胞的增殖、迁移、侵袭和集落形成，在体内也减少了肿瘤的生长。C-met表达的恢复可部分消除上述作用。我们的研究为PIM1和c-met过表达的肺腺癌患者提供了一种有前景的治疗方法。
The proto-oncogene PIM1 plays essential roles in proliferation, survival, metastasis and drug resistance in hematopoietic and solid tumors. Although PIM1 has been shown to be associated with lymph node metastasis and poor prognosis in non-small cell lung cancer, its underlying molecular mechanisms in this context are still unclear. Here we show that PIM1 is frequently overexpressed in lung adenocarcinomas, and its expression level is associated with c-MET expression and poor clinical outcome. We further demonstrate that PIM1 may regulate c-MET expression via phosphorylation of eukaryotic translation initiation factor 4B (eIF4B) on S406. Depletion of PIM1 decreased cell proliferation, migration, invasion and colony formation in vitro, as well as reduced tumor growth in vivo. And these effects were partially abrogated by restoring of c-MET expression. Our study implicates a promising therapeutic approach in lung adenocarcinoma patients with PIM1 and c-MET over expression.