Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells.
Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells.
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血管相关迁移细胞蛋白与表皮生长因子受体相互作用并增强人非小细胞肺癌细胞的增殖和耐药性
DOI：
10.1016/j.cellsig.2019.05.004
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发表时间：
2019
影响因子：
4.8
通讯作者：
Su Ling
中科院分区：
文献类型：
--
作者：
Yao Shun;Shi Feifei;Wang Yingying;Sun Xiaoyang;Sun Wenbo;Zhang Yifeng;Liu Xianfang;Liu Xiangguo;Su Ling
血管相关迁移细胞蛋白（AAMP）在一些人类癌细胞中表达。以往的研究表明AAMP高表达预示预后不良。但其在非小细胞肺癌（NSCLC）细胞中的生物学作用仍不清楚。在本研究中，我们试图探讨AAMP在NSCLC细胞中的功能。根据我们的研究结果，AAMP敲低抑制肺癌细胞增殖，并抑制肺癌细胞在小鼠异种移植模型中的肿瘤发生。表皮生长因子受体（EGFR）是一种主要的受体酪氨酸激酶（RTK），促进增殖，并在癌症病理学中发挥重要作用。我们发现AAMP与NSCLC细胞中EGFR相互作用，并增强其二聚化和酪氨酸1173磷酸化，从而激活ERK 1/2。此外，我们发现AAMP赋予肺癌细胞对化疗药物如埃克替尼和多柔比星的抗性。总之，我们的数据表明，AAMP从NSCLC的损失抑制肿瘤生长和提高药物敏感性，这些发现具有临床意义，以治疗NSCLC癌症。
Angio-associated migratory cell protein (AAMP) is expressed in some human cancer cells. Previous studies have shown AAMP high expression predicted poor prognosis. But its biological role in non-small cell lung cancer (NSCLC) cells is still unknown. In our present study, we attempted to explore the functions of AAMP in NSCLC cells. According to our findings, AAMP knockdown inhibited lung cancer cell proliferation and inhibited lung cancer cell tumorigenesis in the mouse xenograft model. Epidermal growth factor receptor (EGFR) is a primary receptor tyrosine kinase (RTK) that promotes proliferation and plays an important role in cancer pathology. We found AAMP interacted with EGFR and enhanced its dimerization and phosphorylation at tyrosine 1173 which activated ERK1/2 in NSCLC cells. In addition, we showed AAMP conferred the lung cancer cells resistance to chemotherapeutic agents such as icotinib and doxorubicin. Taken together, our data indicate that loss of AAMP from NSCLC inhibits tumor growth and elevates drug sensitivity, and these findings have clinical implications to treat NSCLC cancers.