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Numblike regulates proliferation, apoptosis, and invasion of lung cancer cell

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Tumor Biology

Abstract

Numblike (Numbl), a conserved homolog of Drosophila Numb, has been proved to be implicated in early development of the nervous system. A recent study also showed that Numbl played an important role in tumorigenesis and invasion by suppressing NF-κB activation. However, the biological role of Numbl remains unknown in lung cancer up to now. To address the expression of Numbl in the lung cancer cell, four lung cancer cell lines (metastatic cell lines NCI-H292, 95-D, and non-metastatic cell lines A549, HCC827) and non-cancerous human bronchial epithelial cells were used to detect the protein expression of Numbl by western blotting. The results in this study indicated that the expression of Numbl was downregulated in human lung cancer cell lines, especially in metastatic cell lines. To investigate the role of Numbl in lung cancer cell proliferation, apoptosis, and invasion, we generated human lung cancer 95-D cell lines in which Numbl was either overexpressed or depleted. Subsequently, the effects of Numbl on the cell viability, cycle, apoptosis, and invasion properties in 95-D cells were determined with MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, flow cytometry analysis, and Transwell invasion assays. The results indicated that Numbl could decrease cell viability, suppress cell proliferation and invasion, and promote cell apoptosis. In addition, we investigated the effects of Numbl on the expression of the following proteins: TRAF6 (tumor necrosis factor receptor-associated factor 6), p-p65 (phosphor-NF-κB), cyclin D1, caspase-3, and matrix metalloproteinase 9 (MMP9). Results showed that Numbl could decrease the expression of TRAF6, p-p65, cyclin D1, and MMP9 and increase the expression of caspase-3. All these results suggested that Numbl might be involved in the inhibition of growth, proliferation, and invasion of 95-D cells, as well as the potentiation of apoptosis of 95-D cells by abrogating TRAF6-induced activation of NF-κB.

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Authors and Affiliations

  1. Department of Cardio-thoracic Surgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China

    Li Yingjie, Tang Jian, Yu Changhai & Li Jingbo

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  1. Li Yingjie
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  2. Tang Jian
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  3. Yu Changhai
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  4. Li Jingbo
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Correspondence to Yu Changhai.

Additional information

Li Yingjie and Tang Jian contributed equally to this work.

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Yingjie, L., Jian, T., Changhai, Y. et al. Numblike regulates proliferation, apoptosis, and invasion of lung cancer cell. Tumor Biol. 34, 2773–2780 (2013). https://doi.org/10.1007/s13277-013-0835-7

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  • DOI: https://doi.org/10.1007/s13277-013-0835-7

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