Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells.
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-kappaB 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.
Lee
Jeng-Woei
JW
Department of Life Sciences, Tzu-Chi University, Hualien 97004, Taiwan. jwlee@mail.tcu.edu.tw
Hsiao
Wei-Ting
WT
Chen
Hsia-Yun
HY
Hsu
Lee-Ping
LP
Chen
Peir-Rong
PR
Lin
Ming-Der
MD
Chiu
Shu-Jun
SJ
Shih
Wen-Ling
WL
Hsu
Yih-Chih
YC
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D062445:Claudin-1; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D016328:NF-kappa B; D049452:Green Fluorescent Proteins; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil