Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway |
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Authors: | Lu Zhe Ding Lei Hong Heng Hoggard John Lu Qun Chen Yan-Hua |
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Institution: | aDepartment of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA;bDepartment of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA;cDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China |
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Abstract: | Tight junctions are the most apical component of the junctional complex critical for epithelial cell barrier and polarity functions. Although its disruption is well documented during cancer progression such as epithelial–mesenchymal transition, molecular mechanisms by which tight junction integral membrane protein claudins affect this process remain largely unknown. In this report, we found that claudin-7 was normally expressed in bronchial epithelial cells of human lungs but was either downregulated or disrupted in its distribution pattern in lung cancer. To investigate the function of claudin-7 in lung cancer cells, we transfected claudin-7 cDNA into NCI-H1299, a human lung carcinoma cell line that has no detectable claudin-7 expression. We found that claudin-7 expressing cells showed a reduced response to hepatocyte growth factor (HGF) treatment, were less motile, and formed fewer foot processes than the control cells did. In addition, cells transfected with claudin-7 dramatically decreased their invasive ability after HGF treatment. These effects were mediated through the MAPK signaling pathway since the phosphorylation level of ERK1/2 was significantly lower in claudin-7 transfected cells than in control cells. PD98059, a selective inhibitor of ERK/MAPK pathway, was able to block the motile effect. Claudin-7 formed stable complexes with claudin-1 and -3 and was able to recruit them to the cell-cell junction area in claudin-7 transfected cells. When control and claudin-7 transfected cells were inoculated into nude mice, claudin-7 expressing cells produced smaller tumors than the control cells. Taken together, our study demonstrates that claudin-7 inhibits cell migration and invasion through ERK/MAPK signaling pathway in response to growth factor stimulation in human lung cancer cells. |
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Keywords: | Claudin-7 Tight junctions Cell migration and invasion ERK1/2 Human lung cancer cells |
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