Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M510721200 on December 16, 2005

J. Biol. Chem., Vol. 281, Issue 7, 4457-4466, February 17, 2006
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
281/7/4457    most recent
M510721200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xu, L.
Right arrow Articles by Deng, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, L.
Right arrow Articles by Deng, X.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Protein Kinase C{iota} Promotes Nicotine-induced Migration and Invasion of Cancer Cells via Phosphorylation of µ- and m-Calpains*

Lijun Xu and Xingming Deng1

From the University of Florida Shands Cancer Center, Departments of Medicine and of Anatomy and Cell Biology, University of Florida, Gainesville, Florida 32610-0232

Nicotine is a major component in cigarette smoke that activates the growth-promoting pathways to facilitate the development of lung cancer. However, it is not clear whether nicotine affects cell motility to facilitate tumor metastasis. Here we discovered that nicotine potently induces phosphorylation of both µ- and m-calpains via activation of protein kinase C{iota} (PKC{iota}), which is associated with accelerated migration and invasion of human lung cancer cells. Purified PKC{iota} directly phosphorylates µ- and m-calpains in vitro. Overexpression of PKC{iota} results in increased phosphorylation of both µ- and m-calpains in vivo. Nicotine also induces activation of c-Src, which is a known PKC{iota} upstream kinase. Treatment of cells with the {alpha}7 nicotinic acetylcholine receptor inhibitor {alpha}-bungarotoxin can block nicotine-induced calpain phosphorylation with suppression of calpain activity, wound healing, cell migration, and invasion, indicating that nicotine-induced calpain phosphorylation occurs, at least in part, through a signaling pathway involving the upstream {alpha}7 nicotinic acetylcholine receptor. Intriguingly, depletion of PKC{iota} by RNA interference suppresses nicotine-induced calpain phosphorylation, calpain activity, cell migration, and invasion, indicating that PKC{iota} is a necessary component in nicotine-mediated cell motility signaling. Importantly, nicotine potently induces secretion of µ- and m-calpains from lung cancer cells into culture medium, which may have potential to cleave substrates in the extracellular matrix. These findings reveal a novel role for PKC{iota} as a nicotine-activated, physiological calpain kinase that directly phosphorylates and activates calpains, leading to enhanced migration and invasion of human lung cancer cells.


Received for publication, September 30, 2005 , and in revised form, December 2, 2005.

* This work was supported by NCI, National Institutes of Health Grant R01CA112183-01 and a Flight Attendant Medical Research Institute Clinical Innovator Award (to X. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: University of Florida Shands Cancer Center, 1600 SW Archer Rd., Academic Research Bldg., R4-216, P. O. Box 100232, Gainesville, FL 32610-0232. Tel.: 352-392-9232; Fax: 352-392-5802; E-mail: xdeng{at}ufscc.ufl.edu.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Appl. Physiol.Home page
M. Lehti, R. Kivela, P. Komi, J. Komulainen, H. Kainulainen, and H. Kyrolainen
Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains
J Appl Physiol, April 1, 2009; 106(4): 1419 - 1424.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. Guo, S. Ibaragi, T. Zhu, L.-Y. Luo, G.-F. Hu, P. S. Huppi, and C. Y. Chen
Nicotine Promotes Mammary Tumor Migration via a Signaling Cascade Involving Protein Kinase C and cdc42
Cancer Res., October 15, 2008; 68(20): 8473 - 8481.
[Abstract] [Full Text] [PDF]


Home page
Exp. Biol. Med.Home page
N. Lu, Y. Ling, Y. Gao, Y. Chen, R. Mu, Q. Qi, W. Liu, H. Zhang, H. Gu, S. Wang, et al.
Endostar Suppresses Invasion Through Downregulating the Expression of Matrix Metalloproteinase-2/9 in MDA-MB-435 Human Breast Cancer Cells
Experimental Biology and Medicine, August 1, 2008; 233(8): 1013 - 1020.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
Q. Zhang, X. Tang, Z.-F. Zhang, R. Velikina, S. Shi, and A. D. Le
Nicotine Induces Hypoxia-Inducible Factor-1{alpha} Expression in Human Lung Cancer Cells via Nicotinic Acetylcholine Receptor Mediated Signaling Pathways
Clin. Cancer Res., August 15, 2007; 13(16): 4686 - 4694.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
P. Gailly, F. De Backer, M. Van Schoor, and J. M. Gillis
In situ measurements of calpain activity in isolated muscle fibres from normal and dystrophin-lacking mdx mice
J. Physiol., August 1, 2007; 582(3): 1261 - 1275.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
L. Xu and X. Deng
Suppression of Cancer Cell Migration and Invasion by Protein Phosphatase 2A through Dephosphorylation of {micro}- and m-Calpains
J. Biol. Chem., November 17, 2006; 281(46): 35567 - 35575.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement