HuR is exported to the cytoplasm in oral cancer cells in a different manner from that of normal cells.
HuR, a ubiquitously expressed member of the Hu protein family that binds and stabilizes an AU-rich element (ARE)-containing mRNAs, is known to shuttle between the nucleus and the cytoplasm via several export pathways. When normal cells were treated with heat shock, HuR was exported to the cytoplasm in a chromosome maintenance region 1 (CRM1)-dependent manner. However, in this study, we demonstrate that HuR is exported to the cytoplasm in oral cancer cells even if the cells were treated with the inhibitor of the CRM1-independent export pathway. Immunohistochemical and biochemical analyses showed that HuR existed in both the cytoplasm and the nucleus in oral cancer cells, such as HSC-3 and Ca9.22, but existed entirely inside the nucleus in normal cells. AU-rich element-mRNAs were also exported to the cytoplasm and stabilised in the oral cancer cells, which were inhibited by HuR knockdown. This export of HuR was not affected by at least 7 h of treatment of leptomycin B (LMB), which is an inhibitor of the CRM1-dependent export pathway. These findings suggest that HuR is exported to the cytoplasm in oral carcinoma cells in a different manner from that of normal cells, and is likely to occur through the perturbation of a normal export pathway.
Hasegawa
H
H
Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, North 13 West 7, Kita-ku, Sapporo 060-8586, Japan.
Kakuguchi
W
W
Kuroshima
T
T
Kitamura
T
T
Tanaka
S
S
Kitagawa
Y
Y
Totsuka
Y
Y
Shindoh
M
M
Higashino
F
F
D000935:Antifungal Agents / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005887:Gingival Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000097606:Exportin 1 Protein
D000935:Antifungal Agents; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C098770:ELAVL1 protein, human; C038753:leptomycin B