HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-8113comv1 21/14/3853    most recent 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 Google Scholar Articles by Boudreau, F. Articles by Perreault, N. PubMed PubMed Citation Articles by Boudreau, F. Articles by Perreault, N.

Loss of cathepsin L activity promotes claudin-1 overexpression and intestinal neoplasia

François Boudreau^*,1, Carine R. Lussier^*, Sébastien Mongrain^*, Mathieu Darsigny^*, Julie L. Drouin^*, Geneviève Doyon^*, Eun Ran Suh, Jean-François Beaulieu^*, Nathalie Rivard^* and Nathalie Perreault^*

^* Département d’Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, CIHR Team on Digestive Epithelium, Sherbrooke, Québec, Canada; and

Department of Medicine, GI Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA

¹Correspondence: Département d’Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, 3001 12e ave Nord, Fleurimont, QC, Canada, J1H 5N4. E-mail: francois.boudreau{at}usherbrooke.ca

Intestinal epithelial integrity and polarity are maintained by cohesive interactions between cells via the formation of tight junctions. Irregularities in tight junctions have only recently been found to be associated with the initiation and progression of intestinal neoplasia. The claudin family of proteins is integral to the structure and function of the tight junction but little is known of the molecular events that regulate the expression of these components. The present report identifies cathepsin L, classically a lysosomal cysteine protease, as being induced during intestinal epithelial cell polarization and differentiation. Inhibition of intracellular cathepsin L activity results in the accumulation of disorganized cell layers and a decline in the expression of differentiation markers in cultured intestinal epithelial cells. This coincides with a rapid up-regulation of claudin-1 protein accumulation. Mutant mice defective in cathepsin L activity (furless) display an elevated level of intestinal claudin-1 and claudin-2 expression. Loss of cathepsin L activity leads to a marked increase in tumor multiplicity in the intestine of Apc^Min mice. Given the traditionally viewed biological role of cathepsin L in the processing of lysosomal content as well as in pathological extracellular matrix remodeling, the results here demonstrate an as yet unsuspected intracellular role for this protease in normal intestinal epithelial polarization and initiation of neoplasia.—Boudreau, F., Lussier, C. R., Mongrain, S., Darsigny, M., Drouin, J. L., Doyon, G., Suh, E. R., Beaulieu, J.-F., Rivard, N., Perreault, N. Loss of cathepsin L activity promotes claudin-1 overexpression and intestinal neoplasia.

Key Words: tight junction • polarization • intestinal epithelium

This article has been cited by other articles:

				C. R. Lussier, J.-P. Babeu, B. A. Auclair, N. Perreault, and F. Boudreau Hepatocyte nuclear factor-4{alpha} promotes differentiation of intestinal epithelial cells in a coculture system Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G418 - G428. [Abstract] [Full Text] [PDF]