Upregulated claudin‐1 expression confers resistance to cell death of nasopharyngeal carcinoma cells

• Published in: International journal of cancer Vol. 126; no. 6; pp. 1353 - 1366
• Main Authors: Lee, Jeng‐Woei, Hsiao, Wei‐Ting, Chen, Hsia‐Yun, Hsu, Lee‐Ping, Chen, Peir‐Rong, Lin, Ming‐Der, Chiu, Shu‐Jun, Shih, Wen‐Ling, Hsu, Yih‐Chih
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2010; Wiley-Blackwell
• Subjects: Antimetabolites, Antineoplastic - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Blotting, Western; Cadherins - genetics; Cadherins - metabolism; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Claudin-1; Culture Media, Serum-Free - pharmacology; Drug Resistance, Neoplasm - genetics; E‐cadherin; Fluorouracil - pharmacology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy, Confocal; nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; Otorhinolaryngology. Stomatology; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Tumors; Up-Regulation; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Claudin 1; nasopharyngeal carcinoma; Nasopharynx cancer; Cell adhesion molecule; Malignant tumor; Nasopharynx carcinoma; E-cadherin; Resistance; Cancerology; Cell death; ENT disease; Pharynx disease; claudin-1; E Cadherin; Cancer; Apoptosis
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.24857

Accumulating evidence reveals that aberrant expression of claudins manifests in various tumors; however, their biological functions are poorly understood. Here, we report on the elevated expression of claudin‐1 in nasopharyngeal carcinoma (NPC) cell lines under serum deprivation or fluorouracil (5‐FU) treatment. Interestingly, an increase in expression of claudin‐1 considerably reduced apoptosis rather than enhancing cell proliferation. However, claudin‐1 expression and activity were unaffected by external stimuli or Akt and NF‐κB activation. Notably, predominant cytoplasmic and nuclear localization of claudin‐1 in NPC cells reflected the aforementioned feature. On the other hand, loss of epithelial morphology and E‐cadherin expression was associated with serum withdrawal in NPC cells. Interestingly, restoration of E‐cadherin inhibited the protein elevation and antiapoptotic activity of claudin‐1. In conclusion, our data demonstrate the regulation and novel biological function of claudin‐1 and indicate the important role of claudin‐1 in NPC tumorigenesis.