title: Fascin protein is critical for transforming growth factor β protein-induced invasion and filopodia formation in spindle-shaped tumor cells.
abstract: Fascin, an actin-bundling protein overexpressed in all carcinomas, has been associated with poor prognosis, shorter survival, and more metastatic diseases. It is believed that fascin facilitates tumor metastasis by promoting the formation of invasive membrane protrusions. However, the mechanisms by which fascin is overexpressed in tumors are not clear. TGFβ is a cytokine secreted by tumor and mesenchymal cells and promotes metastasis in many late stage tumors. The pro-metastasis mechanisms of TGFβ remain to be fully elucidated. Here we demonstrated that TGFβ induced fascin expression in spindle-shaped tumor cells through the canonical Smad-dependent pathway. Fascin was critical for TGFβ-promoted filopodia formation, migration, and invasion in spindle tumor cells. More importantly, fascin expression significantly correlates with TGFβ1 and TGFβ receptor I levels in a cohort of primary breast tumor samples. Our results indicate that elevated TGFβ level in the tumor microenvironment may be responsible for fascin overexpression in some of the metastatic tumors. Our data also suggest that fascin could play a central role in TGFβ-promoted tumor metastasis.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Sun
authors.forename: Huifang
authors.initials: H
authors.lastname: He
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiong
authors.forename: Shuang
authors.initials: S
authors.lastname: Lu
authors.forename: Junling
authors.initials: J
authors.lastname: Shen
authors.forename: Anna
authors.initials: A
authors.lastname: Cheng
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: Minjung
authors.initials: M
authors.lastname: Kim
authors.forename: Shengyu
authors.initials: S
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D048430:Cell Shape; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C020324:fascin; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I