title: Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer.
abstract: Dynamic instability of the microtubule network modulates processes such as cell division and motility, as well as cellular morphology. Overexpression of the microtubule-destabilizing phosphoprotein stathmin is frequent in human malignancies and represents a promising therapeutic target. Although stathmin inhibition gives rise to antineoplastic effects, additional and functionally redundant microtubule-interacting proteins may attenuate the efficiency of this therapeutic approach. We have systematically analyzed the expression and potential protumorigenic effects of stathmin family members in human non-small cell lung cancer (NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues and induced tumor cell proliferation, migration, and matrix invasion in respective cell lines. Accordingly, reduced stathmin and SCLIP levels affected cell morphology and were associated with a less malignant phenotype. Combined inhibition of both factors caused additive effects on tumor cell motility, indicating partial functional redundancy. Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. Our results indicate that the coordinated overexpression of microtubule-destabilizing factors by FBP-1 is a critical step to facilitate microtubule dynamics and subsequently increases proliferation and motility of tumor cells.
authors.affiliation: Institute of Pathology, University of Heidelberg, Thoraxklinik Heidelberg, University of Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Singer
authors.forename: Mona
authors.initials: M
authors.lastname: Malz
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Michaela
authors.initials: M
authors.lastname: Bissinger
authors.forename: Martina
authors.initials: M
authors.lastname: Keith
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.forename: Georg
authors.initials: G
authors.lastname: Gdynia
authors.forename: Volker
authors.initials: V
authors.lastname: Ehemann
authors.forename: Philipp Albert
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Kuner
authors.forename: Peter
authors.initials: P
authors.lastname: Huber
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Kai
authors.initials: K
authors.lastname: Breuhahn
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D050777:Stathmin / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C493995:STMN1 protein, human; C112285:STMN3 protein, human; D050777:Stathmin; D004265:DNA Helicases