High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer
High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer
复制标题
PTPRM高表达预示宫颈癌预后不良并促进肿瘤生长和淋巴结转移
DOI：
10.1038/s41419-020-02826-x
复制
发表时间：
2020-08-11
影响因子：
9
通讯作者：
Yao, Shuzhong
中科院分区：
文献类型：
--
作者：
Liu, Pan;Zhang, Chunyu;Yao, Shuzhong
宫颈癌(CCA)伴淋巴结转移(LNM)患者的预后很差。阐明LNM的分子机制可能为CCA合并LNM患者提供临床治疗策略。然而，CCA中LNM的确切机制仍不清楚。在此，我们证明了从TCGA数据集中鉴定的蛋白酪氨酸磷酸酶受体M型(PTPRM)在合并LNM的CCA中显著上调，并与LNM相关。在多因素Cox比例风险模型分析中，PTPRM是CCA患者的独立预后因素，与预后不良相关。此外，通过功能获得和功能丧失的方法，我们发现PTPRM促进CCA细胞的增殖、迁移、侵袭、淋巴管生成和LNM。机制上，PTPRM通过Src-AKT信号通路促进上皮-间充质转化(EMT)，并通过依赖血管内皮生长因子-C(VEGF-C)的方式诱导淋巴管生成，从而导致CCA的LNM。重要的是，PTPRM基因的敲除在体内显著减少了LNM，提示PTPRM在CCA的LNM中起着重要作用。综上所述，我们的发现揭示了颈总动脉LNM的一种新的分子机制，并确认PTPRM是CCA LNM的一个新的预后因素和潜在的治疗靶点。
The prognosis for cervical cancer (CCa) patients with lymph node metastasis (LNM) is dismal. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa patients with LNM. However, the precise mechanism of LNM in CCa remains unclear. Herein, we demonstrated that protein tyrosine phosphatase receptor type M (PTPRM), identified from TCGA dataset, was markedly upregulated in CCa with LNM and correlated with LNM. Moreover, PTPRM was an independent prognostic factor of CCa patients in multivariate Cox′s proportional hazards model analysis and associated with poor prognosis. Furthermore, through gain-of-function and loss-of-function approaches, we found that PTPRM promoted CCa cells proliferation, migration, invasion, lymphangiogenesis, and LNM. Mechanistically, PTPRM promoted epithelial–mesenchymal transition (EMT) via Src-AKT signaling pathway and induced lymphangiogenesis in a VEGF-C dependent manner, resulting in LNM of CCa. Importantly, knockdown of PTPRM dramatically reduced LNM in vivo, suggesting that PTPRM plays an important role in the LNM of CCa. Taken together, our findings uncover a novel molecular mechanism in the LNM of CCa and identify PTPRM as a novel prognostic factor and potential therapeutic target for LNM in CCa.