CDC42-interacting protein 4 promotes metastasis of nasopharyngeal carcinoma by mediating invadopodia formation and activating EGFR signaling.
CDC42-interacting protein 4 promotes metastasis of nasopharyngeal carcinoma by mediating invadopodia formation and activating EGFR signaling.
复制标题
CDC42相互作用蛋白4通过介导侵袭伪足形成和激活EGFR信号传导促进鼻咽癌转移。
DOI：
10.1186/s13046-016-0483-z
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发表时间：
2017-01-28
期刊：
影响因子：
--
通讯作者：
Qian CN
中科院分区：
文献类型：
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作者：
Meng DF;Xie P;Peng LX;Sun R;Luo DH;Chen QY;Lv X;Wang L;Chen MY;Mai HQ;Guo L;Guo X;Zheng LS;Cao L;Yang JP;Wang MY;Mei Y;Qiang YY;Zhang ZM;Yun JP;Huang BJ;Qian CN
鼻咽癌（NPC）是中国南方和东南亚地区的常见恶性肿瘤。在本研究中，我们研究了 CDC42 相互作用蛋白 4 (CIP4) 影响 NPC 的功能和分子机制。通过Western blot、qRT-PCR或IHC检查CIP4的表达水平。采用MTT法检测鼻咽癌细胞增殖率。通过基质胶和Transwell实验检测侵袭能力。 BALB/c裸鼠中揭示了NPC细胞的转移能力。我们报告 CIP4 是 NPC 细胞运动和侵袭所必需的。 CIP4 促进 N-WASP 的激活，控制侵袭伪足的形成并激活 EGFR 信号传导，从而诱导下游 MMP2（基质金属蛋白酶 2）上调。此外，CIP4可以通过激活EGFR通路促进鼻咽癌转移。在裸鼠模型中，CIP4 沉默组的远处转移受到显着抑制。 CIP4 高表达是总生存期 (OS) 和无远处转移生存期 (DMFS) 的独立不良预后因素。我们确定了 CIP4 在 NPC 转移中的关键作用，这表明 CIP4 可能是 NPC 患者的潜在治疗靶点。
Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. In this study, we investigated the functional and molecular mechanisms by which CDC42-interacting protein 4 (CIP4) influences NPC. The expression levels of CIP4 were examined by Western blot, qRT-PCR or IHC. MTT assay was used to detect the proliferative rate of NPC cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of NPC cells were revealed in BALB/c nude mice. We report that CIP4 is required for NPC cell motility and invasion. CIP4 promotes the activation of N-WASP that controls invadopodia formation and activates EGFR signaling, which induces downstream MMP2 (matrix metalloproteinase 2) upregulation. In addition, CIP4 could promote NPC metastasis by activating the EGFR pathway. In nude mouse models, distant metastasis was significantly inhibited in CIP4-silenced groups. High CIP4 expression is an independent adverse prognostic factor of overall survival (OS) and distant metastasis-free survival (DMFS). We identify the critical role of CIP4 in metastasis of NPC which suggest that CIP4 may be a potential therapeutic target of NPC patients.