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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 silencing decreased the expression of cyclin D1 and c-Myc(A). Effects of WIP1 silencing on the protein levels of cyclin D1 and c-Myc, the known target genes of Wnt/β-catenin pathway, were analyzed by Western blotting after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B), Effects of WIP1 silencing on the mRNA levels of cyclin D1 and c-Myc were analyzed by RT-PCR after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. GAPDH mRNA levels were used as internal controls. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
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Figure 6: WIP1 silencing decreased the expression of cyclin D1 and c-Myc(A). Effects of WIP1 silencing on the protein levels of cyclin D1 and c-Myc, the known target genes of Wnt/β-catenin pathway, were analyzed by Western blotting after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B), Effects of WIP1 silencing on the mRNA levels of cyclin D1 and c-Myc were analyzed by RT-PCR after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. GAPDH mRNA levels were used as internal controls. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).

Mentions: WIP1 has been reported to regulate neurogenesis during aging via DKK3-dependent regulation of Wnt [21] and play an important role in Wnt signaling pathways [15]. To reveal the signaling pathways that WIP1 regulates MMP-9 and VEGF-C expression, we investigated the effects of WIP1 knockdown on the expression of Wnt/ß-catenin signaling pathway. We found that the protein and mRNA levels of cyclin D1 and c-Myc, the recognized targets of Wnt/β-catenin pathway [22], were significantly decreased in WIP1-silenced ACC-M cells, which was restored by overexpressing WIP1 (Figure 6A and 6B). These results suggested that WIP1 regulates MMP-9 and VEGF-C expression and promotes ACC-M cells migration and invasion at least partly by facilitating Wnt/ß-catenin signaling.


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 silencing decreased the expression of cyclin D1 and c-Myc(A). Effects of WIP1 silencing on the protein levels of cyclin D1 and c-Myc, the known target genes of Wnt/β-catenin pathway, were analyzed by Western blotting after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B), Effects of WIP1 silencing on the mRNA levels of cyclin D1 and c-Myc were analyzed by RT-PCR after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. GAPDH mRNA levels were used as internal controls. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496200&req=5

Figure 6: WIP1 silencing decreased the expression of cyclin D1 and c-Myc(A). Effects of WIP1 silencing on the protein levels of cyclin D1 and c-Myc, the known target genes of Wnt/β-catenin pathway, were analyzed by Western blotting after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. ß-actin loading control is also shown. Representative of three independent experiments was shown. (B), Effects of WIP1 silencing on the mRNA levels of cyclin D1 and c-Myc were analyzed by RT-PCR after control and WIP1-shRNA1with or without WIP1 overexpression vector, were co-cultured with ACC-M cells. GAPDH mRNA levels were used as internal controls. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05).
Mentions: WIP1 has been reported to regulate neurogenesis during aging via DKK3-dependent regulation of Wnt [21] and play an important role in Wnt signaling pathways [15]. To reveal the signaling pathways that WIP1 regulates MMP-9 and VEGF-C expression, we investigated the effects of WIP1 knockdown on the expression of Wnt/ß-catenin signaling pathway. We found that the protein and mRNA levels of cyclin D1 and c-Myc, the recognized targets of Wnt/β-catenin pathway [22], were significantly decreased in WIP1-silenced ACC-M cells, which was restored by overexpressing WIP1 (Figure 6A and 6B). These results suggested that WIP1 regulates MMP-9 and VEGF-C expression and promotes ACC-M cells migration and invasion at least partly by facilitating Wnt/ß-catenin signaling.

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