Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Mol. Cell. Biol. 24 (8): 3526-3535

Copyright © 2004 by the American Society for Microbiology. All rights reserved.

ARK5 Is a Tumor Invasion-Associated Factor Downstream of Akt Signaling

Atsushi Suzuki, Jie Lu, Gen-ichi Kusakai, Atsuhiro Kishimoto, Tsutomu Ogura, and Hiroyasu Esumi*

Investigative Treatment Division, National Cancer Center Research Institute East, Kashiwa, Chiba 277-8577, Japan

Received for publication 29 July 2003. Revision received 29 August 2003. Accepted for publication 14 January 2004.

Abstract: AMP-activated protein kinases (AMPKs) are a class of serine/threonine protein kinases that are activated by an increase in intracellular AMP concentration. They are a sensitive indicator of cellular energy status and have been found to promote tumor cell survival during nutrient starvation. We recently identified a novel AMPK catalytic subunit family member, ARK5, whose activation is directly regulated by Akt, which, in turn, has been reported to be a key player in tumor malignancy. In this study, we attempted to determine whether ARK5 is involved in tumor malignancy under regulation by Akt. Matrigel invasion assays demonstrated that both overexpressed and endogenous ARK5 showed strong activity dependent on Akt. In addition, ARK5 expression induced activation of matrix metalloproteinase 2 (MMP-2) and MMP-9 following new expression of membrane type 1 MMP (MT1-MMP), and the MT1-MMP expression induced by ARK5 was initiated by rapamycin-sensitive signaling. In nude mice, ARK5 expression was associated with a significant increase in tumor growth and significant suppression of necrosis in tumor tissue. Interestingly, only the ARK5-overexpressing PANC-1 cell line (P/ARK) tumor showed invasion and metastasis in nude mice, although Akt was activated in tumors derived from both P/ARK and its parental cell line. We report that a novel AMPK catalytic subunit family member, ARK5, plays a key role in tumor malignancy downstream of Akt.


* Corresponding author. Mailing address: Investigative Treatment Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Phone: 81-4-7134-6880. Fax: 81-4-7134-6859. E-mail: hesumi{at}east.ncc.go.jp.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The regulation and function of the NUAK family.
X. Sun, L. Gao, H.-Y. Chien, W.-C. Li, and J. Zhao (2013)
J. Mol. Endocrinol. 51, R15-R22
   Abstract »    Full Text »    PDF »
AMPK: A Contextual Oncogene or Tumor Suppressor?.
J. Liang and G. B. Mills (2013)
Cancer Res. 73, 2929-2935
   Abstract »    Full Text »    PDF »
Sonic Hedgehog Pathway Promotes Metastasis and Lymphangiogenesis via Activation of Akt, EMT, and MMP-9 Pathway in Gastric Cancer.
Y. A. Yoo, M. H. Kang, H. J. Lee, B.-h. Kim, J. K. Park, H. K. Kim, J. S. Kim, and S. C. Oh (2011)
Cancer Res. 71, 7061-7070
   Abstract »    Full Text »    PDF »
Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway.
I. Nakano, K. Joshi, K. Visnyei, B. Hu, M. Watanabe, D. Lam, E. Wexler, K. Saigusa, Y. Nakamura, D. R. Laks, et al. (2011)
Neuro Oncology 13, 622-634
   Abstract »    Full Text »    PDF »
New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion.
A. Zagorska, M. Deak, D. G. Campbell, S. Banerjee, M. Hirano, S. Aizawa, A. R. Prescott, and D. R. Alessi (2010)
Science Signaling 3, ra25
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans unc-82 Encodes a Serine/Threonine Kinase Important for Myosin Filament Organization in Muscle During Growth.
P. E. Hoppe, J. Chau, K. A. Flanagan, A. R. Reedy, and L. A. Schriefer (2010)
Genetics 184, 79-90
   Abstract »    Full Text »    PDF »
The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis.
G. B. W. Wertheim, T. W. Yang, T.-c. Pan, A. Ramne, Z. Liu, H. P. Gardner, K. D. Dugan, P. Kristel, B. Kreike, M. J. van de Vijver, et al. (2009)
PNAS 106, 15855-15860
   Abstract »    Full Text »    PDF »
RhoC Promotes Metastasis via Activation of the Pyk2 Pathway in Prostate Cancer.
M. Iiizumi, S. Bandyopadhyay, S. K. Pai, M. Watabe, S. Hirota, S. Hosobe, T. Tsukada, K. Miura, K. Saito, E. Furuta, et al. (2008)
Cancer Res. 68, 7613-7620
   Abstract »    Full Text »    PDF »
5'-AMP-Activated Protein Kinase (AMPK) Is Induced by Low-Oxygen and Glucose Deprivation Conditions Found in Solid-Tumor Microenvironments.
K. R. Laderoute, K. Amin, J. M. Calaoagan, M. Knapp, T. Le, J. Orduna, M. Foretz, and B. Viollet (2006)
Mol. Cell. Biol. 26, 5336-5347
   Abstract »    Full Text »    PDF »
NDR2 Acts as the Upstream Kinase of ARK5 during Insulin-like Growth Factor-1 Signaling.
A. Suzuki, T. Ogura, and H. Esumi (2006)
J. Biol. Chem. 281, 13915-13921
   Abstract »    Full Text »    PDF »
Overexpression of c-Maf Contributes to T-Cell Lymphoma in Both Mice and Human.
N. Morito, K. Yoh, Y. Fujioka, T. Nakano, H. Shimohata, Y. Hashimoto, A. Yamada, A. Maeda, F. Matsuno, H. Hata, et al. (2006)
Cancer Res. 66, 812-819
   Abstract »    Full Text »    PDF »
Muscle contractions, AICAR, and insulin cause phosphorylation of an AMPK-related kinase.
J. S. Fisher, J.-S. Ju, P. J. Oppelt, J. L. Smith, A. Suzuki, and H. Esumi (2005)
Am J Physiol Endocrinol Metab 289, E986-E992
   Abstract »    Full Text »    PDF »
Maternal Embryonic Leucine Zipper Kinase/Murine Protein Serine-Threonine Kinase 38 Is a Promising Therapeutic Target for Multiple Cancers.
D. Gray, A. M. Jubb, D. Hogue, P. Dowd, N. Kljavin, S. Yi, W. Bai, G. Frantz, Z. Zhang, H. Koeppen, et al. (2005)
Cancer Res. 65, 9751-9761
   Abstract »    Full Text »    PDF »
Cross-talk between JIP3 and JIP1 during Glucose Deprivation: SEK1-JNK2 AND Akt1 ACT AS MEDIATORS.
J. J. Song and Y. J. Lee (2005)
J. Biol. Chem. 280, 26845-26855
   Abstract »    Full Text »    PDF »
Dissociation of Akt1 from its negative regulator JIP1 is mediated through the ASK1-MEK-JNK signal transduction pathway during metabolic oxidative stress: a negative feedback loop.
J. J. Song and Y. J. Lee (2005)
J. Cell Biol. 170, 61-72
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882