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Claudin‐7 regulates survival and glucose metabolism of human lung cancer cells
Author(s) -
Kim Do Hyung,
Jackson Spencer M,
Chen YanHua,
Lu Qun
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1099.6
Subject(s) - cell culture , claudin , biology , glycogen synthase , cell growth , glycogen , cancer cell , cell , endocrinology , chemistry , medicine , microbiology and biotechnology , tight junction , cancer , biochemistry , genetics
Claudins are a family of tight junction membrane proteins engaged in a variety of human diseases including cancer. It has been reported that lung cancer patients with high claudin‐7 expression showed better survival than those with low claudin‐7 expression. Our study has shown that suppressing claudin‐7 expression (KD) in a human lung adenocarcinoma HCC827 cell line significantly increased cell proliferation in culture and tumor growth in mice. To investigate how tumor microenvironment plays a role in claudin‐7 regulation of cell survival, we treated the control and claudin‐7 KD cells under the hypoxia (1% O 2 ) condition for 3 days. Light microscopic study revealed KD cells with fairly‐normal looking morphology whereas control cells displayed shrunken cell morphology. Immunofluorescence staining confirmed substantially decreased expression of cleaved PARP in KD cells than that of control cells (p < 0.01). To examine how claudin‐7 modulates glucose metabolism for cell survival, the cells were pre‐treated with normal (2g/L) glucose‐containing medium in normal oxygen condition for 2 days, followed by being sub‐cultured with normal or low (0.2g/L) glucose‐containing medium in either hypoxia or normal oxygen condition up to additional 24 hours. Western blot revealed an elevation in phosphorylation (or inhibition) of a negative regulator of glycogen synthesis GSK3β, phospho‐glycogen synthase kinase 3 beta (p‐GSK3β), and a substantial decrease in a cellular energy sensor, phospho‐AMP kinase (p‐AMPK), in KD cells when compared to control cells after the cells were treated in low glucose‐containing media for 24 hours, indicating the enhanced glycogen synthesis in KD cells for cell survival. This observation was not evident when the cells were cultured in the normal oxygen condition. We propose that claudin‐7 participates in regulating glucose metabolism and cell survival in human lung cancer cells through modulating GSK3β and AMPK signaling pathways. Support or Funding Information This study was supported by National Institute of Health grants HL085752.