Fascin protein is critical for transforming growth factor β protein-induced invasion and filopodia formation in spindle-shaped tumor cells

Jianwei Sun, Huifang He, Yin Xiong, Shuang Lu, Junling Shen, Anna Cheng, Wei Chiao Chang, Ming Feng Hou, Johnathan M. Lancaster, Minjung Kim, Shengyu Yang

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 spindleshaped 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.

Original languageEnglish
Pages (from-to)38865-38875
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number45
DOIs
Publication statusPublished - Nov 11 2011
Externally publishedYes

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Pseudopodia
Transforming Growth Factors
Tumors
Cells
Neoplasms
Proteins
Neoplasm Metastasis
Tumor Microenvironment
fascin
Actins
Breast Neoplasms
Cytokines
Carcinoma
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Fascin protein is critical for transforming growth factor β protein-induced invasion and filopodia formation in spindle-shaped tumor cells. / Sun, Jianwei; He, Huifang; Xiong, Yin; Lu, Shuang; Shen, Junling; Cheng, Anna; Chang, Wei Chiao; Hou, Ming Feng; Lancaster, Johnathan M.; Kim, Minjung; Yang, Shengyu.

In: Journal of Biological Chemistry, Vol. 286, No. 45, 11.11.2011, p. 38865-38875.

Research output: Contribution to journalArticle

Sun, Jianwei ; He, Huifang ; Xiong, Yin ; Lu, Shuang ; Shen, Junling ; Cheng, Anna ; Chang, Wei Chiao ; Hou, Ming Feng ; Lancaster, Johnathan M. ; Kim, Minjung ; Yang, Shengyu. / Fascin protein is critical for transforming growth factor β protein-induced invasion and filopodia formation in spindle-shaped tumor cells. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 45. pp. 38865-38875.
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AU - Shen, Junling

AU - Cheng, Anna

AU - Chang, Wei Chiao

AU - Hou, Ming Feng

AU - Lancaster, Johnathan M.

AU - Kim, Minjung

AU - Yang, Shengyu

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