title: FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth.
abstract: The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Finland. Electronic address: minna.peippo@utu.fi.
authors.forename: Minna
authors.initials: M
authors.lastname: Peippo
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland. Electronic address: maria.gardberg@utu.fi.
authors.forename: Maria
authors.initials: M
authors.lastname: Gardberg
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Finland. Electronic address: tarja.lamminen@utu.fi.
authors.forename: Tarja
authors.initials: T
authors.lastname: Lamminen
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Finland. Electronic address: katja.kaipio@utu.fi.
authors.forename: Katja
authors.initials: K
authors.lastname: Kaipio
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: olli.carpen@utu.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Finland. Electronic address: vanina.heuser@utu.fi.
authors.forename: Vanina D
authors.initials: VD
authors.lastname: Heuser
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000199:Actins; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins
keywords: Actin; Cytoskeleton; FHOD1; Formin; MAL; MKL-1; MRTF-A; Melanoma; SRE; Tumorigenesis