Fascin Protein Is Critical for Transforming Growth Factor beta Protein-induced Invasion and Filopodia Formation in Spindle-shaped Tumor Cells

作者：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^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(45): 38865-38875.

DOI：10.1074/jbc.M111.270413

• NEGATIVE BREAST-CANCER
• TGF-BETA
• PROGNOSTIC-SIGNIFICANCE
• METASTASIS
• ACTIN
• CARCINOMA
• EXPRESSION
• MIGRATION
• MOTILITY
• RECEPTOR

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. TGF beta is a cytokine secreted by tumor and mesenchymal cells and promotes metastasis in many late stage tumors. The pro-metastasis mechanisms of TGF beta remain to be fully elucidated. Here we demonstrated that TGF beta induced fascin expression in spindleshaped tumor cells through the canonical Smad-dependent pathway. Fascin was critical for TGF beta-promoted filopodia formation, migration, and invasion in spindle tumor cells. More importantly, fascin expression significantly correlates with TGF beta 1 and TGF beta receptor I levels in a cohort of primary breast tumor samples. Our results indicate that elevated TGF beta 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 TGF beta-promoted tumor metastasis.

• 出版日期2011-11-11
• 单位青岛农业大学