ailure and poor outcome, new treatment options would be more than 22564524 welcome. Invadopodia, actin-rich short-lived membrane protrusions 16260133 in cancer cells, are reminiscent of their more structured and stable counterpart in benign cells, the podosomes. Invadopodia are crucial for degradation of extracellular matrix, as they serve as sites for activation and secretion of matrix metalloproteinases. The proteolytic activity of MMPs contributes to invasive migration. Invadopodia have been identified in several cancer types, including SCC. There is growing evidence that invadopodia formation is a central feature of EMTdriven invasion. Whether formins are involved in the formation of invadopodia has remained an unanswered question. Our results demonstrate for the first time that a formin is involved in both degradation of ECM and the formation of invadopodia. However, it seems that this regulation is indirect, since FHOD1 appeared not to be a component of the invadopodial structures. Implicating clinical relevance, increased FHOD1expression in cancer specimens was not global but restricted to cells with mesenchymal morphology at the invasive front. In conclusion, we recognize FHOD1 as the major formin upregulated in the process of EMT in oral SCC. FHOD1 regulates the alteration of cytoskeletal and functional properties EMT; stress-fibre rich phenotype, efficient migration, proteolysis and invadopodia formation. Importantly, this increase of FHOD1 expression is seen in clinical cancers, in which EMT contributes to dissemination of tumours and subsequent treatment failure. In this setting, the activation cascade of FHOD1 could serve as a potential drug target. Whether increased expression of FHOD1 occurs in SCC in other locations or other types of cancer in general, is an important question that remains to be addressed. mental, and native species and are thought to not only be the most important group of pathogens of dicotyledonous plants but also often the source of yield reduction in cereal crop species. Some of the most damaging oomycete genera are Aphanomyces, Peronospora, Phytophthora, Plasmopara, Pseudoperonospora, and Pythium species; the wide host range of these genera, coupled with the diversity of diseases they cause, pose a challenge to the development of durable disease control strategies in plants. Within the oomycetes, Pythium species belongs to the peronosporalean lineage that includes hemibiotrophic Phytophthora species and the obligate biotrophic Hyaloperonospora species. The genus Pythium comprises more than 250 described species with 50% of these accepted by the community and currently classified into 11 phylogenetic clades. Recently, one of these clades was shown to be closer to Phytophthora and the new genus Phytopythium has been described but Cyanidin 3-O-glucoside chloride official renaming of all Pythium species in clade K has not yet occurred. Most Pythium species are saprobes or facultative plant pathogens causing a wide variety of diseases, including seed rots and damping-off, root, stem and fruit Comparative Oomycete Genomics rots, foliar blights, and postharvest decay. Some Pythium species have been reported to be parasitic to fungi and a few have been evaluated for biological control against other oomycete plant pathogens. Some Pythium species are parasites of insects, fish, algae and at least one species, Pythium insidiosum, infects mammals including humans. Members of the genus Pythium differ from other oomycetes, including Phytophthora species, in ailure and poor outcome, new treatment options would be more than welcome. Invadopodia, actin-rich short-lived membrane protrusions in cancer cells, are reminiscent of their more structured and stable counterpart in benign cells, the podosomes. Invadopodia are crucial for degradation of extracellular matrix, as they serve as sites for activation and secretion of matrix metalloproteinases. The proteolytic activity of MMPs contributes to invasive migration. Invadopodia have been identified in several cancer types, including SCC. There is growing evidence that invadopodia formation is a central feature of EMTdriven invasion. Whether formins are involved in the formation of invadopodia has remained an unanswered question. Our results demonstrate for the first time that a formin is involved in both degradation of ECM and the formation of invadopodia. However, it seems that this regulation is indirect, since FHOD1 appeared not to be a component of the invadopodial structures. Implicating clinical 
relevance, increased FHOD1expression in cancer specimens was not global but restricted to cells with mesenchymal morphology at the invasive front. In conclusion, we recognize FHOD1 as the major formin upregulated in the process of EMT in oral SCC. FHOD1 regulates the alteration of cytoskeletal and functional properties EMT; stress-fibre rich phenotype, efficient migration, proteolysis and invadopodia formation. Importantly, this increase of FHOD1 expression is seen in clinical cancers, in which EMT contributes to dissemination of tumours and subsequent treatment failure. In 7510605 this setting, the activation cascade of FHOD1 could serve as a potential drug target. Whether increased expression of FHOD1 occurs in SCC in other locations or other types of cancer in general, is an important question that remains to be addressed. mental, and native species and are thought to not only be the most important group of pathogens of dicotyledonous plants but also often the source of yield reduction in cereal crop species. Some of the most damaging oomycete genera are Aphanomyces, Peronospora, Phytophthora, Plasmopara, Pseudoperonospora, and Pythium species; the wide host range of these genera, coupled with the diversity of diseases they cause, pose a challenge to 12931192 the development of durable disease control strategies in plants. Within the oomycetes, Pythium species belongs to the peronosporalean lineage that includes hemibiotrophic Phytophthora species and the obligate biotrophic Hyaloperonospora species. The genus Pythium comprises more than 250 described species with 50% of these accepted by the community and currently classified into 11 phylogenetic clades. Recently, one of these clades was shown to be closer to Phytophthora and the new genus Phytopythium has been described but official renaming of all Pythium species in clade K has not yet occurred. Most Pythium species are saprobes or facultative plant pathogens causing a wide variety of diseases, including seed rots and damping-off, root, stem and fruit Comparative Oomycete Genomics rots, foliar blights, and postharvest decay. Some Pythium species have been reported to be parasitic to fungi and a few have been evaluated for biological control against other oomycete plant pathogens. Some Pythium species are parasites of insects, fish, algae and at least one species, Pythium insidiosum, infects mammals including humans. Members of the genus Pythium differ from other oomycetes, including Phytophthora species, in
