title: Stathmin activity influences sarcoma cell shape, motility, and metastatic potential.
abstract: The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent of microtubule dynamics, which is implicated in many cellular processes, including adhesion, migration, and morphology. Among the destabilizing proteins, stathmin is overexpressed in different human malignancies and has been recently linked to the regulation of cell motility. The observation that stathmin was overexpressed in human recurrent and metastatic sarcomas prompted us to investigate stathmin contribution to tumor local invasiveness and distant dissemination. We found that stathmin stimulated cell motility in and through the extracellular matrix (ECM) in vitro and increased the metastatic potential of sarcoma cells in vivo. On contact with the ECM, stathmin was negatively regulated by phosphorylation. Accordingly, a less phosphorylable stathmin point mutant impaired ECM-induced microtubule stabilization and conferred a higher invasive potential, inducing a rounded cell shape coupled with amoeboid-like motility in three-dimensional matrices. Our results indicate that stathmin plays a significant role in tumor metastasis formation, a finding that could lead to exploitation of stathmin as a target of new antimetastatic drugs.
authors.affiliation: Division of Experimental Oncology 2, Division of Pathology, and Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS Aviano 33081, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Belletti
authors.forename: Milena S
authors.initials: MS
authors.lastname: Nicoloso
authors.forename: Monica
authors.initials: M
authors.lastname: Schiappacassi
authors.forename: Stefania
authors.initials: S
authors.lastname: Berton
authors.forename: Francesca
authors.initials: F
authors.lastname: Lovat
authors.forename: Katarina
authors.initials: K
authors.lastname: Wolf
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.forename: Sara
authors.initials: S
authors.lastname: D'Andrea
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Peter
authors.initials: P
authors.lastname: Friedl
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baldassarre
mesh_terms: D000818:Animals; D001681:Biological Assay; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D002999:Clone Cells; D005109:Extracellular Matrix / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D010766:Phosphorylation; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D050777:Stathmin; D014404:Tubulin