Involvement of microtubule-associated protein 2 (MAP2) in oral cancer cell motility: A novel biological function of MAP2 in non-neuronal cells
Involvement of microtubule-associated protein 2 (MAP2) in oral cancer cell motility: A novel biological function of MAP2 in non-neuronal cells
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DOI：
10.1016/j.bbrc.2007.11.179
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发表时间：
2008-02-08
影响因子：
3.1
通讯作者：
Chen, Jeff Yi-Fu
中科院分区：
文献类型：
--
作者：
Liu, Shyun-Yeu;Chen, Yi-Ting;Chen, Jeff Yi-Fu
微管相关蛋白 2 (MAP2) 因其在神经元发育过程中神经突生长中的明确作用而闻名。然而，MAP2在非神经元细胞例如上皮细胞中的生物学功能仍然很大程度上未知。在本研究中，我们试图通过分别建立两种 MAP2 亚型 MAP2A 和 MAP2C 在口腔鳞状细胞癌 Ca9-22 中的稳定表达来研究 MAP2 的细胞功能。 MAP2A 或 MAP2C 的异位表达导致微管主要在细胞外周聚集。值得注意的是，MAP2A（而非 MAP2C）的过表达显着促进 Ca9-22 细胞的迁移，而通过特定 siRNA 寡核苷酸敲低 MAP2A 表达可显着降低 HaCaT（一种具有丰富内源性 MAP2A 的永生化角质形成细胞系）的细胞迁移。此外，通过免疫组织化学研究，MAP2A 显示在侵袭性口腔癌组织中高度且选择性地表达，这与其通过体外测定揭示的其促进运动的细胞功能一致。因此，我们的研究结果不仅确定了 MAP2 在非神经元细胞中的新作用，而且首次提供了 MAP2 在恶性口腔癌组织中的意义。 (c) 2007 Elsevier Inc. 保留所有权利。
Microtubule-associated protein 2 (MAP2) has been better known for its well-defined role primarily in neurite outgrowth during neuronal development. However, the biological functions of MAP2 in non-neuronal cells, such as epithelia] cells, remain largely unknown. In the present study, we sought to investigate the cellular functions of MAP2 by separately establishing stable expression of two MAP2 isoforms, MAP2A and MAP2C, in oral squamous cell carcinoma, Ca9-22. Ectopic expression of MAP2A or MAP2C results in microtubule bundling predominantly at the cell periphery. Remarkably, overexpression of MAP2A but not MAP2C significantly promotes migration of Ca9-22 cells, whereas knockdown of MAP2A expression by specific siRNA oligos dramatically decreases cell migration of HaCaT, an immortalized keratinocyte cell line with abundant endogenous MAP2A. Furthermore, by immunohistochemical studies, MAP2A was shown to highly and selectively express in invasive oral cancer tissues, consistent with its motility-promoting cellular function revealed through in vitro assays. Thus, our findings have not only identified a novel role of MAP2 in non-neuronal cells, but also provided the first implication of MAP2 in malignant oral cancer tissues. (c) 2007 Elsevier Inc. All rights reserved.