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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 enhances cell migration and invasion of T47D cells.(A) Graphic representation of the migratory capability of stably transfected T47D cells expressing either Twist or control vector assessed using a wound healing assay. A scratch (“wound”) was inflicted to a cell layer produced 48 hours post-plating, and culture continued for an additional 24 hrs. Wound closures were photographed at 0 and 24 hr. Presented data are the mean ± SD from three independent experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 50 μm. (B) Graphic representation of the invasiveness of T47D cells stably expressing Twist or control vector using a modified Boyden Chamber invasion assay as described in the Materials and Methods. Presented data are the mean ± SD from three separate experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 100 μm.
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f4: Overexpression of Twist enhances cell migration and invasion of T47D cells.(A) Graphic representation of the migratory capability of stably transfected T47D cells expressing either Twist or control vector assessed using a wound healing assay. A scratch (“wound”) was inflicted to a cell layer produced 48 hours post-plating, and culture continued for an additional 24 hrs. Wound closures were photographed at 0 and 24 hr. Presented data are the mean ± SD from three independent experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 50 μm. (B) Graphic representation of the invasiveness of T47D cells stably expressing Twist or control vector using a modified Boyden Chamber invasion assay as described in the Materials and Methods. Presented data are the mean ± SD from three separate experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 100 μm.

Mentions: To investigate the migratory and invasive capabilities mediated by Twist, we performed an in vitro wound healing assay, which is commonly used to assess the effects of exogenous gene expression on the migration of individual cells. Closure of the scratch wound required significantly less time in T47D-Twist cells than in vector control cells (Fig. 4A). Statistical analysis indicated that migration activity of T47D-Twist cells was about 3-fold higher than that of vector control cells (Fig. 4A). We also used Matrigel-coated Boyden chambers to assess cell invasiveness; the invasion capacity of T47D-Twist cells increased 14-fold compared with that of vector control cells (Fig. 4B).


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 enhances cell migration and invasion of T47D cells.(A) Graphic representation of the migratory capability of stably transfected T47D cells expressing either Twist or control vector assessed using a wound healing assay. A scratch (“wound”) was inflicted to a cell layer produced 48 hours post-plating, and culture continued for an additional 24 hrs. Wound closures were photographed at 0 and 24 hr. Presented data are the mean ± SD from three independent experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 50 μm. (B) Graphic representation of the invasiveness of T47D cells stably expressing Twist or control vector using a modified Boyden Chamber invasion assay as described in the Materials and Methods. Presented data are the mean ± SD from three separate experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Overexpression of Twist enhances cell migration and invasion of T47D cells.(A) Graphic representation of the migratory capability of stably transfected T47D cells expressing either Twist or control vector assessed using a wound healing assay. A scratch (“wound”) was inflicted to a cell layer produced 48 hours post-plating, and culture continued for an additional 24 hrs. Wound closures were photographed at 0 and 24 hr. Presented data are the mean ± SD from three independent experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 50 μm. (B) Graphic representation of the invasiveness of T47D cells stably expressing Twist or control vector using a modified Boyden Chamber invasion assay as described in the Materials and Methods. Presented data are the mean ± SD from three separate experiments, with *indicates p < 0.01 when comparing with control values. A representative experiment is shown in the right panel. Scale bars, 100 μm.
Mentions: To investigate the migratory and invasive capabilities mediated by Twist, we performed an in vitro wound healing assay, which is commonly used to assess the effects of exogenous gene expression on the migration of individual cells. Closure of the scratch wound required significantly less time in T47D-Twist cells than in vector control cells (Fig. 4A). Statistical analysis indicated that migration activity of T47D-Twist cells was about 3-fold higher than that of vector control cells (Fig. 4A). We also used Matrigel-coated Boyden chambers to assess cell invasiveness; the invasion capacity of T47D-Twist cells increased 14-fold compared with that of vector control cells (Fig. 4B).

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