Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer.
We investigated gene expression profiles of non-small cell lung carcinomas (NSCLC) to screen candidate molecules that might be useful as diagnostic markers or for development of novel molecular-targeting therapies. Here we report evidence that a member of the armadillo protein family, plakophilin 3 (PKP3), is a potential molecular target for treatment of lung cancers and might also serve as a prognostic indicator. We documented elevated expression of PKP3 in the great majority of NSCLC samples examined. Treatment of NSCLC cells with small interfering RNAs of PKP3 suppressed growth of the cancer cells; on the other hand, induction of exogenous expression of PKP3 conferred growth-promoting activity on COS-7 cells and enhanced their mobility in vitro. To investigate its function, we searched for PKP3-interacting proteins and identified dynamin 1-like, which was also activated in NSCLC. In addition, a high level of PKP3 expression was associated with poor survival as well as disease stage and node status for patients with lung adenocarcinoma, suggesting an important role of the protein in development and progression of this disease. As our data imply that up-regulation of PKP3 is a frequent and important feature of lung carcinogenesis, we suggest that targeting the PKP3 molecule might hold promise for development of a new therapeutic and diagnostic strategy for clinical management of lung cancers.
Furukawa
Chiyuki
C
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo.
Daigo
Yataro
Y
Ishikawa
Nobuhisa
N
Kato
Tatsuya
T
Ito
Tomoo
T
Tsuchiya
Eiju
E
Sone
Saburo
S
Nakamura
Yusuke
Y
D000818:Animals; D019556:COS Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002522:Chlorocebus aethiops; D018450:Disease Progression; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D051191:Plakophilins; D011379:Prognosis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C495339:PKP3 protein, human; D051191:Plakophilins; D011506:Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins