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Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway.

Wang Y, Liu J, Ying X, Lin PC, Zhou BP - Sci Rep (2016)

Bottom Line: However, the mechanisms that facilitate the functions of Twist remain unclear.Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ.Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, Zhejiang, 310007, China.

ABSTRACT
Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular de-differentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.

No MeSH data available.


Related in: MedlinePlus

Overexpression of Twist induces CSC-like properties in T47D cells.(A) Graphic representation of cell growth rates by T47D cells stably expressing Twist or control vector. Cell counts were obtained daily over a 4 day period. Presented data are the mean ± SD from two independent experiments with triplicate samples. NS stands for statistically non-significant. (B) Tumorsphere formation was assessed in T47D cells overexpressing Twist under normoxic or hypoxic conditions. Representative images of tumorspheres are shown in the right panel. Scale bars, 100 μm. Left panel, are graphic representations of tumorsphere number. Presented data are the percentage of control vector values, with mean ± SD of three separate experiments performed in duplicate. #p <  0.05 and *p <  0.01 when vector control cells compared with their Twist-expressing clones, respectively.
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f3: Overexpression of Twist induces CSC-like properties in T47D cells.(A) Graphic representation of cell growth rates by T47D cells stably expressing Twist or control vector. Cell counts were obtained daily over a 4 day period. Presented data are the mean ± SD from two independent experiments with triplicate samples. NS stands for statistically non-significant. (B) Tumorsphere formation was assessed in T47D cells overexpressing Twist under normoxic or hypoxic conditions. Representative images of tumorspheres are shown in the right panel. Scale bars, 100 μm. Left panel, are graphic representations of tumorsphere number. Presented data are the percentage of control vector values, with mean ± SD of three separate experiments performed in duplicate. #p <  0.05 and *p <  0.01 when vector control cells compared with their Twist-expressing clones, respectively.

Mentions: To investigate whether Twist-expression affects proliferation of breast cancer cells, we measured cell growth of T47D-Twist cells by cell counting. T47D-Twist cells did not demonstrate a significant growth difference compared with the vector control cells over the 96-hour interval examined (Fig. 3A). We also examined tumorsphere formation of these cells, which is based on the unique property of stem/progenitor cells to survive and grow in serum-free suspension. Although both T47D-vector and T47D-Twist cell types did form tumorspheres, the size and density of tumorspheres formed by T47D-Twist cells were lightly smaller than those formed by vector control cells under normoxic conditions. Under hypoxic conditions, tumorspheres were sparse in vector control cells. Surprisingly, the size and density of tumorsphere formed by T47D-Twist cells were much bigger than that of control cells (Fig. 3B). These results suggest that expression of Twist promotes induction of CSC-like properties and their growth in T47D cells under hypoxic conditions.


Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway.

Wang Y, Liu J, Ying X, Lin PC, Zhou BP - Sci Rep (2016)

Overexpression of Twist induces CSC-like properties in T47D cells.(A) Graphic representation of cell growth rates by T47D cells stably expressing Twist or control vector. Cell counts were obtained daily over a 4 day period. Presented data are the mean ± SD from two independent experiments with triplicate samples. NS stands for statistically non-significant. (B) Tumorsphere formation was assessed in T47D cells overexpressing Twist under normoxic or hypoxic conditions. Representative images of tumorspheres are shown in the right panel. Scale bars, 100 μm. Left panel, are graphic representations of tumorsphere number. Presented data are the percentage of control vector values, with mean ± SD of three separate experiments performed in duplicate. #p <  0.05 and *p <  0.01 when vector control cells compared with their Twist-expressing clones, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837350&req=5

f3: Overexpression of Twist induces CSC-like properties in T47D cells.(A) Graphic representation of cell growth rates by T47D cells stably expressing Twist or control vector. Cell counts were obtained daily over a 4 day period. Presented data are the mean ± SD from two independent experiments with triplicate samples. NS stands for statistically non-significant. (B) Tumorsphere formation was assessed in T47D cells overexpressing Twist under normoxic or hypoxic conditions. Representative images of tumorspheres are shown in the right panel. Scale bars, 100 μm. Left panel, are graphic representations of tumorsphere number. Presented data are the percentage of control vector values, with mean ± SD of three separate experiments performed in duplicate. #p <  0.05 and *p <  0.01 when vector control cells compared with their Twist-expressing clones, respectively.
Mentions: To investigate whether Twist-expression affects proliferation of breast cancer cells, we measured cell growth of T47D-Twist cells by cell counting. T47D-Twist cells did not demonstrate a significant growth difference compared with the vector control cells over the 96-hour interval examined (Fig. 3A). We also examined tumorsphere formation of these cells, which is based on the unique property of stem/progenitor cells to survive and grow in serum-free suspension. Although both T47D-vector and T47D-Twist cell types did form tumorspheres, the size and density of tumorspheres formed by T47D-Twist cells were lightly smaller than those formed by vector control cells under normoxic conditions. Under hypoxic conditions, tumorspheres were sparse in vector control cells. Surprisingly, the size and density of tumorsphere formed by T47D-Twist cells were much bigger than that of control cells (Fig. 3B). These results suggest that expression of Twist promotes induction of CSC-like properties and their growth in T47D cells under hypoxic conditions.

Bottom Line: However, the mechanisms that facilitate the functions of Twist remain unclear.Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ.Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, Zhejiang, 310007, China.

ABSTRACT
Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular de-differentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.

No MeSH data available.


Related in: MedlinePlus