S100A14 inhibits proliferation of oral carcinoma derived cells through G1-arrest.
Altered expression of S100A14 has been reported in various human cancers including oral squamous cell carcinomas (OSCCs). Its biological functions in carcinogenesis, however, are largely unknown. This study aimed to investigate the functional role of S100A14 in tumor cell proliferation and its possible functional association with p53. S100A14 protein was found to be gradually down-regulated during the transition from normal to dysplastic and carcinoma cells in an in vitro human OSCC progression model. When over-expressed by employing retroviral expression vector, S100A14 inhibited proliferation of CaLH3 and OSCC1, OSCC cell-lines harboring wild type (wt) p53, by inducing G1-arrest. This G1-arrest correlated with up-regulation of p21 both in the CaLH3 and OSCC1 cell-lines. shRNA mediated silencing of p53 led to partial suppression of p21 in S100A14 over-expressing CaLH3 cells, indicating that p21 up-regulation was, at least, partly dependent on p53. We further demonstrated that nuclear accumulation of p53 occurred with over-expression of S100A14 in CaLH3 cells. Our data suggest a novel role of S100A14 in OSCC cell proliferation by inducing G1-arrest and also indicate a functional link between S100A14 and the tumor suppressor protein p53.
Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, N5009 Bergen, Norway. Dipak.Sapkota@gades.uib.no
Dipak
D
Sapkota
Daniela Elena
DE
Costea
Magnus
M
Blø
Ove
O
Bruland
James B
JB
Lorens
Endre N
EN
Vasstrand
Salah O
SO
Ibrahim
D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C462950:S100A14 protein, human; D016159:Tumor Suppressor Protein p53