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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

MMP-9 and VEGF-C were downstream targets of WIP1 in vivo and WIP1 expression was associated with the poorer prognosis of ACC patients(A), Stable WIP1-shRNA1 ACC-M cells were subcutaneously injected into nude mice. Individual tumor volume was measured at the 7th week after injection and growth curve of xenograft tumors was shown. (B), Western blotting and RT-PCR analysis of the protein and mRNA levels of MMP-9 and VEGF-C in shRNA-neg, WIP1-shRNA1 and control group. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05). (C), WIP1 expression was associated with invasive subtypes of human ACC. Representative images of the immunohistochemical staining of WIP1 in ACC samples. C left, WIP1 in normal human salivary tissue. C middle, WIP1 in weak tumor staining. C right, WIP1 in strong tumor staining. Original magnification, × 100; inset, × 200; bar, 100 mm. (D), Kaplan-Meier survival analysis in patients with ACC. Overexpression of WIP1 in ACC was associated with a shorter overall survival in the respective group.
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Figure 5: MMP-9 and VEGF-C were downstream targets of WIP1 in vivo and WIP1 expression was associated with the poorer prognosis of ACC patients(A), Stable WIP1-shRNA1 ACC-M cells were subcutaneously injected into nude mice. Individual tumor volume was measured at the 7th week after injection and growth curve of xenograft tumors was shown. (B), Western blotting and RT-PCR analysis of the protein and mRNA levels of MMP-9 and VEGF-C in shRNA-neg, WIP1-shRNA1 and control group. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05). (C), WIP1 expression was associated with invasive subtypes of human ACC. Representative images of the immunohistochemical staining of WIP1 in ACC samples. C left, WIP1 in normal human salivary tissue. C middle, WIP1 in weak tumor staining. C right, WIP1 in strong tumor staining. Original magnification, × 100; inset, × 200; bar, 100 mm. (D), Kaplan-Meier survival analysis in patients with ACC. Overexpression of WIP1 in ACC was associated with a shorter overall survival in the respective group.

Mentions: Finally, we established xenograft using cells treated respectively with shRNA-neg, shRNA1 and control, and documented the tumor volume weekly. As shown in Figure 5A right, there was no difference of tumor volume between the shRNA1 and the shRNA-neg groups in the first two weeks, but the growth of the tumor in the shRNA1 group significantly slowed down since the 4th week, compared with the shRNA-neg group (p < 0.05).


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)

MMP-9 and VEGF-C were downstream targets of WIP1 in vivo and WIP1 expression was associated with the poorer prognosis of ACC patients(A), Stable WIP1-shRNA1 ACC-M cells were subcutaneously injected into nude mice. Individual tumor volume was measured at the 7th week after injection and growth curve of xenograft tumors was shown. (B), Western blotting and RT-PCR analysis of the protein and mRNA levels of MMP-9 and VEGF-C in shRNA-neg, WIP1-shRNA1 and control group. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05). (C), WIP1 expression was associated with invasive subtypes of human ACC. Representative images of the immunohistochemical staining of WIP1 in ACC samples. C left, WIP1 in normal human salivary tissue. C middle, WIP1 in weak tumor staining. C right, WIP1 in strong tumor staining. Original magnification, × 100; inset, × 200; bar, 100 mm. (D), Kaplan-Meier survival analysis in patients with ACC. Overexpression of WIP1 in ACC was associated with a shorter overall survival in the respective group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: MMP-9 and VEGF-C were downstream targets of WIP1 in vivo and WIP1 expression was associated with the poorer prognosis of ACC patients(A), Stable WIP1-shRNA1 ACC-M cells were subcutaneously injected into nude mice. Individual tumor volume was measured at the 7th week after injection and growth curve of xenograft tumors was shown. (B), Western blotting and RT-PCR analysis of the protein and mRNA levels of MMP-9 and VEGF-C in shRNA-neg, WIP1-shRNA1 and control group. Error bars represent the mean ± SD of triplicate experiments (*p < 0.05). (C), WIP1 expression was associated with invasive subtypes of human ACC. Representative images of the immunohistochemical staining of WIP1 in ACC samples. C left, WIP1 in normal human salivary tissue. C middle, WIP1 in weak tumor staining. C right, WIP1 in strong tumor staining. Original magnification, × 100; inset, × 200; bar, 100 mm. (D), Kaplan-Meier survival analysis in patients with ACC. Overexpression of WIP1 in ACC was associated with a shorter overall survival in the respective group.
Mentions: Finally, we established xenograft using cells treated respectively with shRNA-neg, shRNA1 and control, and documented the tumor volume weekly. As shown in Figure 5A right, there was no difference of tumor volume between the shRNA1 and the shRNA-neg groups in the first two weeks, but the growth of the tumor in the shRNA1 group significantly slowed down since the 4th week, compared with the shRNA-neg group (p < 0.05).

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