RRC ID 51947
著者 Akizuki R, Shimobaba S, Matsunaga T, Endo S, Ikari A.
タイトル Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of phosphorylation of Akt in human lung squamous cell carcinoma.
ジャーナル Biochim Biophys Acta Mol Cell Res
Abstract Abnormal expression of claudin (CLDN) subtypes has been reported in various solid cancers. However, it is unknown which subtype plays a key role in the regulation of proliferation in cancer cells. The expression of CLDN3-5, 7, and 18 in human lung squamous carcinoma tissues was lower than that in normal tissue. Here, we examined which combination of exogenous CLDNs expression inhibits proliferation and the molecular mechanism using human lung squamous RERF-LC-AI cells. Real-time polymerase chain reaction and western blotting showed that CLDN3-5, 7, and 18 are little expressed in RERF-LC-AI cells. In the exogenously transfected cells, CLDN5, 7, and 18 were distributed in the cell-cell contact areas concomitant with ZO-1, a tight junctional scaffolding protein, whereas CLDN3 and 4 were not. Cell proliferation was individually and additively suppressed by CLDN5, 7, and 18. The expression of these CLDNs showed no cytotoxicity compared with mock cells. CLDN5, 7, and 18 increased p21 and decreased cyclin D1, resulting in the suppression of cell cycle G1-S transition. The expression of these CLDNs inhibited phosphorylation of Akt without affecting phosphorylated ERK1/2. Furthermore, these CLDNs inhibited the nuclear localization of Akt and its association with 3-phosphoinositide-dependent protein kinase-1 (PDK1). The suppression of G1-S transition caused by CLDN5, 7, and 18 was rescued by the expression of constitutively active-Akt. We suggest that the reduction of CLDN5, 7, and 18 expression loses the suppressive ability of interaction between PDK1 and Akt and causes sustained phosphorylation of Akt, resulting in the disordered proliferation in lung squamous carcinoma cells.
巻・号 1864(2)
ページ 293-302
公開日 2017-2-1
DOI 10.1016/j.bbamcr.2016.11.018
PII S0167-4889(16)30305-6
PMID 27884700
MeSH Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Cycle / physiology Cell Line, Tumor Cell Proliferation / physiology* Claudin-5 / genetics Claudin-5 / physiology* Claudins / genetics Claudins / physiology* Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology Phosphorylation Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics Signal Transduction
IF 4.739
引用数 22
リソース情報
ヒト・動物細胞 RERF-LC-AI(RCB0444)