Li Yang, Francia Giulio, Zhang Jian-Ying
Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA.
Oncotarget. 2015 Oct 20;6(32):32656-68. doi: 10.18632/oncotarget.5328.
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.
p62/IMP2是一种癌胚蛋白，在多种癌症中过表达，是胰岛素样生长因子2 mRNA结合蛋白家族的成员。我们之前报道过，与健康个体相比，癌症患者血清中存在高水平的p62/IMP2自身抗体。在此，我们报告104例人类乳腺癌中有72例肿瘤组织中p62/IMP2过表达，以及患者血清中存在高水平的p62/IMP2自身抗体（216例中有63例）。为了探究p62/IMP2在乳腺癌进展中的作用，我们构建了两个人类乳腺癌细胞系（MDA-MB-231和LM2-4）的p62/IMP2转染变体。通过体外实验，我们发现p62/IMP2过表达可增加细胞迁移，并降低细胞与细胞外基质（ECM）蛋白的黏附。对我们构建的变体进行了人类细胞外基质和黏附分子qPCR阵列检测，结果鉴定出一组mRNA，其表达随p62/IMP2过表达而改变，其中包括结缔组织生长因子（CTGF）mRNA——我们证明它是p62/IMP2的结合伴侣。总体而言，我们的研究结果为p62/IMP2促进乳腺癌进展的分子机制提供了新的见解。
