CD147-CD98hc Complex Contributes to Poor Prognosis of Non-Small Cell Lung Cancer Patients Through Promoting Cell Proliferation Via the PI3K/Akt Signaling Pathway
CD147-CD98hc Complex Contributes to Poor Prognosis of Non-Small Cell Lung Cancer Patients Through Promoting Cell Proliferation Via the PI3K/Akt Signaling Pathway
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CD147-CD98hc 复合物通过 PI3K/Akt 信号通路促进细胞增殖，导致非小细胞肺癌患者预后不良
DOI：
10.1245/s10434-014-3816-1
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发表时间：
2014-12-01
影响因子：
3.7
通讯作者：
Xing, Jinliang
中科院分区：
文献类型：
--
作者：
Fei, Fei;Li, Xiaofei;Xing, Jinliang
背景CD147和CD98重链(CD98hc)在多种肿瘤的细胞膜上形成复合体，但该复合体是否存在于非小细胞肺癌(NSCLC)细胞中并影响患者的预后尚不清楚。分析CD147、CD98hc表达与非小细胞肺癌患者预后的关系。结果CD147和CD98hc在非小细胞肺癌细胞中的表达均显著上调，且两者的表达水平显著相关(P<0.001)。免疫荧光染色和免疫共沉淀显示CD147和CD98hc在NSCLC细胞上可形成复合体。与携带CD147−/CD98hc−的非小细胞肺癌患者相比，携带CD147+/CD98hc+的患者总体生存率(OS)显著降低，危险性比(HR)为1.92(P=0.010)，复发危险性显著增加(HR为1.97，P=0.004)。此外，我们还证明了CD147-CD98hc复合体的敲除和强制表达显著影响了肺癌细胞系的增殖。Western印迹分析表明，CD147和CD98hc的表达下调和过表达显著影响NSCLC细胞Akt的磷酸化。结论CD147-CD98hc复合体通过PI3K/Akt通路促进细胞增殖，从而导致NSCLC患者预后不良。
BackgroundIt has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated.MethodsThe expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation.ResultsBoth CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p< 0.001). Immunoflurenece staining and co-immunoprecipitation demonstrated that CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147−/CD98hc−, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p= 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p= 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc.ConclusionsOur findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.