p62/IMP2 stimulates cell migration and reduces cell adhesion in breast cancer.
p62/IMP2 stimulates cell migration and reduces cell adhesion in breast cancer.
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DOI：
10.18632/oncotarget.5328
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发表时间：
2015-10-20
期刊：
影响因子：
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通讯作者：
Zhang JY
中科院分区：
文献类型：
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作者：
Li Y;Francia G;Zhang JY
p62/IMP 2是一种在几种类型的癌症中过表达的癌胚蛋白，并且是胰岛素样生长因子2 mRNA结合蛋白家族的成员。我们以前报道过，高水平的p62/IMP 2自身抗体存在于癌症患者的血清中，与健康人相比。在此，我们报告了104例人乳腺癌中72例肿瘤组织中p62/IMP 2的过度表达，以及患者血清中高水平的p62/IMP 2自身抗体（216例中有63例）。为了探索p62/IMP 2在乳腺癌进展中的作用，我们产生了两种人乳腺癌细胞系的p62/IMP 2转染变体：MDA-MB-231和LM 2 -4。使用体外分析，我们发现p62/IMP 2的过表达可以增加细胞迁移，并减少细胞与细胞外基质（ECM）蛋白的粘附。使用我们生成的变体进行了人细胞外基质和粘附分子qPCR阵列，并鉴定了一组表达随p62/IMP 2过表达而改变的mRNA，包括结缔组织生长因子（CTGF）mRNA -我们证明其是p62/IMP 2结合伴侣。总的来说，我们的研究结果为p62/IMP 2促进乳腺癌进展的分子机制提供了新的见解。
p62/IMP2 is an oncofetal protein that is overexpressed in several types of cancer, and is a member of the family of insulin-like growth factor 2 mRNA binding proteins. We previously reported that high levels of p62/IMP2 autoantibody are present in sera from cancer patients, compared to healthy individuals. Here, we report the overexpression of p62/IMP2 in tumor tissues of 72 out of 104 cases of human breast cancer, and high levels of p62/IMP2 autoantibody in patients’ sera (in 63 out of 216 cases). To explore the role of p62/IMP2 in breast cancer progression, we generated p62/IMP2 transfected variants of two human breast cancer cell lines: MDA-MB-231 and LM2-4. Using in vitro assays we found that overexpression of p62/IMP2 can increase cell migration, and reduce cell adhesion to extracellular matrix (ECM) proteins. A Human Extracellular Matrix and Adhesion Molecules qPCR array was performed with our generated variants, and it identified a group of mRNAs whose expression was altered with p62/IMP2 overexpression, including connective tissue growth factor (CTGF) mRNA – which we show to be a p62/IMP2 binding partner. Overall, our results provide new insights into the molecular mechanism by which p62/IMP2 can contribute to breast cancer progression.