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Carcinogenesis Advance Access published online on January 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp022
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells

Franck Bazile1, Aude Pascal1, Isabelle Arnal2, Christophe Le Clainche3, Franck Chesnel1 and Jacek Z. Kubiak1,*

1 CNRS UMR 6061, Institute of Genetics & Development, Mitosis & Meiosis Group, University of Rennes 1, IFR 150 GFAS, Faculty of Medicine, Rennes, France
2 Equipe Tubulin and Interacting Proteins, UMR 6026 CNRS/University of Rennes 1, Rennes, France
3 CNRS, Laboratoire d'Enzymologie et Biochimie Structurales, FRE 2930 CNRS, Gif s.Yvette, France

* To whom correspondence should be addressed: Tel: 33-(0)2.23.46.98.78; Fax : 33-(0)2.23.23.44.78; E-mail: Jacek.Kubiak{at}univ-rennes1.fr

Translationally Controlled Tumor-associated Protein (TCTP) is a ubiquitous and highly conserved protein implicated in cancers. Here we demonstrate that interactions of TCTP with microtubules (MTs) are functionally important but indirect, and we reveal novel interaction of TCTP with the actin cytoskeleton. Firstly, immunofluorescence in Xenopus XL2 cells revealed cytoplasmic fibers stained with TCTP but not with tubulin antibodies, as well as MT-free of TCTP. Furthermore, TCTP localized to a subset of actin-rich fibers in migrating cells. Secondly XlTCTP did not affect in vitro assembly/disassembly of MTs, and lacked MT binding affinity both in pull-down assays and in cell-free extracts. Although TCTP also failed to bind to purified F-actin, it associated with microfilaments in cell-free extracts. Thirdly, TCTP concentrated in mitotic spindle did not colocalize with MTs, and was easily dissociated from these structures except at the poles. Finally, RNAi knockdown of TCTP in XL2 and HeLa cells provoked drastic, MT-dependent, shape change. These data show that although TCTP interacts with MTs it does not behave as classic MT Associated Protein (MAP). Our evidence for an association of TCTP with F-actin structures, and for an involvement in cell shape regulation, implicates this protein in integrating cytoskeletal interations both in interphase and mitosis providing a new avenue to fully understand the role of TCTP.

Received September 3, 2008; revised December 24, 2008; accepted January 11, 2009.


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