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WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C.

Tang YL, Liu X, Gao SY, Feng H, Jiang YP, Wang SS, Yang J, Jiang J, Ma XR, Tang YJ, Chen Y, Liang XH - Oncotarget (2015)

Bottom Line: The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers.Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells.In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.

ABSTRACT
The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

No MeSH data available.


Related in: MedlinePlus

WIP1 modulates cell migration and invasion by regulating MMP-9 and VEGF-C expression(A), Western blotting analysis of WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. WIP1 silencing and overexpression were determined by Western blotting. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B and C), The quantitative analysis of migration (B) and invasion (C) in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells. Representative images of migrated and invaded cells were shown under inverted microscopy. The mean was derived from cell counts of 5 fields, and each experiment was repeated 3 times. (D), Western blotting analysis of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (E), Transcription levels of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells, relative to GAPDH, determined by quantitative RT-PCR. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
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Figure 3: WIP1 modulates cell migration and invasion by regulating MMP-9 and VEGF-C expression(A), Western blotting analysis of WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. WIP1 silencing and overexpression were determined by Western blotting. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B and C), The quantitative analysis of migration (B) and invasion (C) in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells. Representative images of migrated and invaded cells were shown under inverted microscopy. The mean was derived from cell counts of 5 fields, and each experiment was repeated 3 times. (D), Western blotting analysis of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (E), Transcription levels of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells, relative to GAPDH, determined by quantitative RT-PCR. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).

Mentions: To further verify whether the effect of WIP1 knockdown on the reduction of migration and invasion of ACC-M cells is unique, we transfected the pcDNA3 plasmid WIP1 vector in WIP1 silencing cells, as confirmed by immunoblotting (Figure 3A) and real-time PCR. We also observed that the up-regulation of WIP1 expression restored ACC-M cell migration and invasion (Figure 3B and 3C) and the protein and mRNA levels of MMP-9 and VEGF-C were added by approximately 65% and 70%, respectively, in WIP1-restored cells, compared with control cells (Figure 3D and 3E). As controls, the protein and mRNA levels of the MMP-2, MMP-13, and VEGF-D did not alter under these conditions.


WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C.

Tang YL, Liu X, Gao SY, Feng H, Jiang YP, Wang SS, Yang J, Jiang J, Ma XR, Tang YJ, Chen Y, Liang XH - Oncotarget (2015)

WIP1 modulates cell migration and invasion by regulating MMP-9 and VEGF-C expression(A), Western blotting analysis of WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. WIP1 silencing and overexpression were determined by Western blotting. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B and C), The quantitative analysis of migration (B) and invasion (C) in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells. Representative images of migrated and invaded cells were shown under inverted microscopy. The mean was derived from cell counts of 5 fields, and each experiment was repeated 3 times. (D), Western blotting analysis of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (E), Transcription levels of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells, relative to GAPDH, determined by quantitative RT-PCR. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 3: WIP1 modulates cell migration and invasion by regulating MMP-9 and VEGF-C expression(A), Western blotting analysis of WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. WIP1 silencing and overexpression were determined by Western blotting. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B and C), The quantitative analysis of migration (B) and invasion (C) in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells. Representative images of migrated and invaded cells were shown under inverted microscopy. The mean was derived from cell counts of 5 fields, and each experiment was repeated 3 times. (D), Western blotting analysis of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1-shRNA1 ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (E), Transcription levels of MMP-9, VEGF-C, MMP-2, MMP-13, and VEGF-D in WIP1-pcDNA co-cultured with WIP1 -shRNA1 ACC-M cells, relative to GAPDH, determined by quantitative RT-PCR. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
Mentions: To further verify whether the effect of WIP1 knockdown on the reduction of migration and invasion of ACC-M cells is unique, we transfected the pcDNA3 plasmid WIP1 vector in WIP1 silencing cells, as confirmed by immunoblotting (Figure 3A) and real-time PCR. We also observed that the up-regulation of WIP1 expression restored ACC-M cell migration and invasion (Figure 3B and 3C) and the protein and mRNA levels of MMP-9 and VEGF-C were added by approximately 65% and 70%, respectively, in WIP1-restored cells, compared with control cells (Figure 3D and 3E). As controls, the protein and mRNA levels of the MMP-2, MMP-13, and VEGF-D did not alter under these conditions.

Bottom Line: The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers.Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells.In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.

ABSTRACT
The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

No MeSH data available.


Related in: MedlinePlus