This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Furukawa, C. Articles by Nakamura, Y. Search for Related Content PubMed PubMed Citation Articles by Furukawa, C. Articles by Nakamura, Y.

Plakophilin 3 Oncogene as Prognostic Marker and Therapeutic Target for Lung Cancer

¹ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo; ² Department of Internal Medicine and Molecular Therapeutics, The University of Tokushima School of Medicine, Tokushima; ³ Department of Surgical Pathology, Hokkaido University Hospital, Sapporo; and ⁴ Kanagawa Cancer Center Research Institute, Kanagawa, Japan

Requests for reprints: Yusuke Nakamura, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5372; Fax: 81-3-5449-5433; E-mail: yusuke{at}ims.u-tokyo.ac.jp.

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.

This article has been cited by other articles:

				A. Takano, N. Ishikawa, R. Nishino, K. Masuda, W. Yasui, K. Inai, H. Nishimura, H. Ito, H. Nakayama, Y. Miyagi, et al. Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer Cancer Res., August 15, 2009; 69(16): 6694 - 6703. [Abstract] [Full Text] [PDF]

				D. Hirata, T. Yamabuki, D. Miki, T. Ito, E. Tsuchiya, M. Fujita, M. Hosokawa, K. Chayama, Y. Nakamura, and Y. Daigo Involvement of Epithelial Cell Transforming Sequence-2 Oncoantigen in Lung and Esophageal Cancer Progression Clin. Cancer Res., January 1, 2009; 15(1): 256 - 266. [Abstract] [Full Text] [PDF]

				T. Kato, N. Sato, A. Takano, M. Miyamoto, H. Nishimura, E. Tsuchiya, S. Kondo, Y. Nakamura, and Y. Daigo Activation of Placenta-Specific Transcription Factor Distal-less Homeobox 5 Predicts Clinical Outcome in Primary Lung Cancer Patients Clin. Cancer Res., April 15, 2008; 14(8): 2363 - 2370. [Abstract] [Full Text] [PDF]

				N. Ishikawa, A. Takano, W. Yasui, K. Inai, H. Nishimura, H. Ito, Y. Miyagi, H. Nakayama, M. Fujita, M. Hosokawa, et al. Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas Cancer Res., December 15, 2007; 67(24): 11601 - 11611. [Abstract] [Full Text] [PDF]

				P. P. Luedi, F. S. Dietrich, J. R. Weidman, J. M. Bosko, R. L. Jirtle, and A. J. Hartemink Computational and experimental identification of novel human imprinted genes Genome Res., December 1, 2007; 17(12): 1723 - 1730. [Abstract] [Full Text] [PDF]

				M. Taniwaki, A. Takano, N. Ishikawa, W. Yasui, K. Inai, H. Nishimura, E. Tsuchiya, N. Kohno, Y. Nakamura, and Y. Daigo Activation of KIF4A as a Prognostic Biomarker and Therapeutic Target for Lung Cancer Clin. Cancer Res., November 15, 2007; 13(22): 6624 - 6631. [Abstract] [Full Text] [PDF]

				S. Hayama, Y. Daigo, T. Yamabuki, D. Hirata, T. Kato, M. Miyamoto, T. Ito, E. Tsuchiya, S. Kondo, and Y. Nakamura Phosphorylation and Activation of Cell Division Cycle Associated 8 by Aurora Kinase B Plays a Significant Role in Human Lung Carcinogenesis Cancer Res., May 1, 2007; 67(9): 4113 - 4122. [Abstract] [Full Text] [PDF]

				T. Yamabuki, A. Takano, S. Hayama, N. Ishikawa, T. Kato, M. Miyamoto, T. Ito, H. Ito, Y. Miyagi, H. Nakayama, et al. Dikkopf-1 as a Novel Serologic and Prognostic Biomarker for Lung and Esophageal Carcinomas Cancer Res., March 15, 2007; 67(6): 2517 - 2525. [Abstract] [Full Text] [PDF]

				C. Suzuki, K. Takahashi, S. Hayama, N. Ishikawa, T. Kato, T. Ito, E. Tsuchiya, Y. Nakamura, and Y. Daigo Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer Mol. Cancer Ther., February 1, 2007; 6(2): 542 - 551. [Abstract] [Full Text] [PDF]

				T. Kato, S. Hayama, T. Yamabuki, N. Ishikawa, M. Miyamoto, T. Ito, E. Tsuchiya, S. Kondo, Y. Nakamura, and Y. Daigo Increased Expression of Insulin-like Growth Factor-II Messenger RNA-Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer Clin. Cancer Res., January 15, 2007; 13(2): 434 - 442. [Abstract] [Full Text] [PDF]

				S. Hayama, Y. Daigo, T. Kato, N. Ishikawa, T. Yamabuki, M. Miyamoto, T. Ito, E. Tsuchiya, S. Kondo, and Y. Nakamura Activation of CDCA1-KNTC2, Members of Centromere Protein Complex, Involved in Pulmonary Carcinogenesis Cancer Res., November 1, 2006; 66(21): 10339 - 10348. [Abstract] [Full Text] [PDF]

				K. Takahashi, C. Furukawa, A. Takano, N. Ishikawa, T. Kato, S. Hayama, C. Suzuki, W. Yasui, K. Inai, S. Sone, et al. The Neuromedin U-Growth Hormone Secretagogue Receptor 1b/Neurotensin Receptor 1 Oncogenic Signaling Pathway as a Therapeutic Target for Lung Cancer Cancer Res., October 1, 2006; 66(19): 9408 - 9419. [Abstract] [Full Text] [PDF]

				C. Suzuki, Y. Daigo, N. Ishikawa, T. Kato, S. Hayama, T. Ito, E. Tsuchiya, and Y. Nakamura ANLN Plays a Critical Role in Human Lung Carcinogenesis through the Activation of RHOA and by Involvement in the Phosphoinositide 3-Kinase/AKT Pathway Cancer Res., December 15, 2005; 65(24): 11314 - 11325. [Abstract] [Full Text] [PDF]