Suppression of claudin-7 enhances human lung cancer cell survival

Abstract

Claudin-7 belongs to a group of tight junction membrane proteins that play vital roles in many human diseases including human lung cancer. Lung cancer is noted to be the leading cause of cancer death for both men and women in the United States, with statistics reporting mortality rates as high as 85% and five-year survival rates as low as 15%. Lung cancer is especially prominent in North Carolina. Our current study focuses on the role of claudin-7 in human lung cancer cell survival under the exposure of tumor microenvironment. Hypoxia is one of the tumor microenvironment conditions and plays an important role in cancer progression. To achieve the hypoxia condition, HCC827 human lung cancer cells with normal claudin-7 expression (control) or with claudin-7 knockdown (KD) were treated with 1% O2 (hypoxic) for 3 days. The cell counting assay showed that the percentage of dead cells were significantly lower in KD cells compared to that of control cells. The immunofluorescent staining analysis also supported our finding through depicting the decreased expression of cleaved PARP in KD cells than that in the control cells (p<0.05). Reduced cleaved PARP expression means the cell survival is better since the cleaved PARP signal is activated in cell apoptosis. Western blot results further confirmed that the suppression of claudin-7 promoted cancer cell survival and reduced cell apoptosis. These results support our hypothesis that claudin-7 has a tumor suppression role in human lung cancer growth and suppression of claudin-7 enhances lung cancer cell survival under tumor microenvironment hypoxia condition through inhibiting cell apoptosis. This study is supported by 2015 Undergraduate Research and Creative Activity Award from ECU Division of Research and Graduate Studies.