Stathmin activity influences sarcoma cell shape, motility, and metastatic potential.
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.
Belletti
Barbara
B
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.
Nicoloso
Milena S
MS
Schiappacassi
Monica
M
Berton
Stefania
S
Lovat
Francesca
F
Wolf
Katarina
K
Canzonieri
Vincenzo
V
D'Andrea
Sara
S
Zucchetto
Antonella
A
Friedl
Peter
P
Colombatti
Alfonso
A
Baldassarre
Gustavo
G
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
D050505:Mutant Proteins; D050777:Stathmin; D014404:Tubulin