QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 19, 2008
doi: 10.1242/10.1242/jcs.022038

This Article Figures Only 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 Google Scholar Articles by Maxwell, C. A. Articles by Turley, E. PubMed PubMed Citation Articles by Maxwell, C. A. Articles by Turley, E.

Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?

¹ Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet, Barcelona, Spain
² University of Minnesota, Department of Laboratory Medicine and Pathology, Minnesota Comprehensive Cancer Center, Minneapolis, MN, USA
³ London Regional Cancer Program, London Health Sciences, Department of Oncology/Biochemistry, University of Western Ontario, London ON N6A 4L6, Canada

^* Authors for correspondence (e-mail: cmaxwell{at}ico.scs.es; eva.turley{at}lhsc.on.ca)

Accepted 9 February 2008

Tumor cells use a wide variety of post-translational mechanisms to modify the functional repertoire of their transcriptome. One emerging but still understudied mechanism involves the export of cytoplasmic proteins that then partner with cell-surface receptors and modify both the surface-display kinetics and signaling properties of these receptors. Recent investigations demonstrate moonlighting roles for the proteins epimorphin, FGF1, FGF2, PLK1 and Ku80, to name a few, during oncogenesis and inflammation. Here, we review the molecular mechanisms of unconventional cytoplasmic-protein export by focusing on the mitotic-spindle/hyaluronan-binding protein RHAMM, which is hyper-expressed in many human tumors. Intracellular RHAMM associates with BRCA1 and BARD1; this association attenuates the mitotic-spindle-promoting activity of RHAMM that might contribute to tumor progression by promoting genomic instability. Extracellular RHAMM-CD44 partnering sustains CD44 surface display and enhances CD44-mediated signaling through ERK1 and ERK2 (ERK1/2); it might also contribute to tumor progression by enhancing and/or activating the latent tumor-promoting properties of CD44. The unconventional export of proteins such as RHAMM is a novel process that modifies the roles of tumor suppressors and promoters, such as BRCA1 and CD44, and might provide new targets for therapeutic intervention.

Key words: CD44, RHAMM (HMMR), Unconventional protein export

This article has been cited by other articles:

				P. Kalab and R. Heald The RanGTP gradient - a GPS for the mitotic spindle J. Cell Sci., May 15, 2008; 121(10): 1577 - 1586. [Abstract] [Full Text] [PDF]