N-WASP is highly expressed in hepatocellular carcinoma and associated with poor prognosis

Jin, Kemin; Lu, Min; Liu, Fangfang; Gu, Jin; Du, Xiaojuan; Xing, Baocai

doi:10.1016/j.surg.2012.08.067

Cited by 23 publications

(25 citation statements)

References 38 publications

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“…The broadly expressed actin polymerizing protein N-WASp, which has previously been implicated in hepatocellular carcinoma, was found to promote trafficking of MT1-MMP into invadopodia and to stabilize it via tethering of its cytoplasmic tail to F-actin, thus ensuring optimum MT1-MMP localization for facilitating ECM degradation [48]. Furthermore, N-WASp depletion led to a 50% reduction in matrix degradation, which is consistent with the effects of N-WASp overexpression [49].…”

Section: Interactions Of Mmps With Pro-invasive Pathwayssupporting

confidence: 76%

Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis

Brown

Murray

2015

The Journal of Pathology

211

144

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The purpose of this review is to highlight the recent mechanistic developments elucidating the role of matrix metalloproteinases (MMPs) in tumour invasion and metastasis. The ability of tumour cells to invade, migrate, and subsequently metastasize is a fundamental characteristic of cancer. Tumour invasion and metastasis are increasingly being characterized by the dynamic relationship between cancer cells and their microenvironment and developing a greater understanding of these basic pathological mechanisms is crucial. While MMPs have been strongly implicated in these processes as a result of extensive circumstantial evidence -for example, increased expression of individual MMPs in tumours and association of specific MMPs with prognosis -the underpinning mechanisms are only now being elucidated. Recent studies are now providing a mechanistic basis, highlighting and reinforcing the catalytic and non-catalytic roles of specific MMPs as key players in tumour invasion and metastasis.

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Section: Interactions Of Mmps With Pro-invasive Pathwayssupporting

confidence: 76%

Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis

Brown

Murray

2015

The Journal of Pathology

211

144

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“…In this study we examined the suitability of the ABPs DIAPH1, N‐WASP, VASP and fascin as such individual targets. These proteins directly regulate the dynamics of the actin cytoskeleton and have been reported to be up‐regulated in several tumor entities . Our data demonstrated that besides cortactin, DIAPH1 showed the highest expression frequency in colorectal carcinoma and revealed a correlation with DIAPH1 expression and colon cancer cell metastasis.…”

Section: Discussionsupporting

confidence: 51%

“…These proteins directly regulate the dynamics of the actin cytoskeleton and have been reported to be up-regulated in several tumor entities. 5,23,[35][36][37] Our data demonstrated that besides cortactin, DIAPH1 showed the highest expression frequency in colorectal carcinoma and revealed a correlation with DIAPH1 expression and colon cancer cell metastasis. In addition, we showed that down-regulation of DIAPH1 expression nearly completely reduced metastasis (by 93%) of colon cancer cells in SCID mice, while knock-down of cortactin expression only reduced metastasis by 70% and the size of micrometastasis formed by cortactin knock-down cells was comparable to those of control cells.…”

Section: Discussionmentioning

confidence: 55%

Expression of DIAPH1 is up‐regulated in colorectal cancer and its down‐regulation strongly reduces the metastatic capacity of colon carcinoma cells

Lin

Izbicki

König

et al. 2013

Intl Journal of Cancer

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In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably downregulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy.Formation of metastasis is a complex process, starting with strong morphological and functional changes of tumor cells.

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“…However, a correlation was not observed between N-WASP expression and overall patient survival. Research by Jin et al [20] also showed that N-WASP was highly expressed in hepatocellular carcinoma and demonstrated its prognostic importance in this disease.…”

Section: Discussionmentioning

confidence: 99%

Expression of Neural Wiskott-Aldrich Syndrome Protein in Clear Cell Renal Cell Carcinoma and Its Correlation with Clinicopathological Features

Liu

Chen²,

Ji³

et al. 2014

Urol Int

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Introduction: Neural Wiskott-Aldrich syndrome protein (N-WASP) expression is associated with tumor cell invasion and migration. However, its expression status in clear cell renal cell carcinoma (CCRCC) remains unclear. We examined the level of N-WASP in CCRCC and its association with clinicopathological features characteristic. Materials and Methods: 73 CCRCC patients who underwent radical nephrectomy or partial nephrectomy were enrolled. Immunohistochemical staining for N-WASP was performed on tissue microarrays constructed from tumor and para-tumor tissue obtained from these patients. The difference in N-WASP expression between tumor tissue and adjacent normal renal tissue was examined. Correlations between N-WASP expression in the tumor and clinicopathological parameters were analyzed and the relationship between N-WASP expression and overall survival also assessed. Uni- and multivariate survival analyses were performed. Results: N-WASP expression was significantly reduced in tumor tissues and was significantly related to the histological grade of CCRCC. A higher level of N-WASP expression in the tumor was associated with relatively poor survival in CCRCC patients. The level of N-WASP expression, age at time of surgery, and histological grade were all responsible for clinical outcome in CCRCC patients. N-WASP was an independent predictor for overall survival. Conclusions: N-WASP was downregulated in CCRCC and could serve as a prognostic biomarker for predicting clinical outcome of CCRCC.

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N-WASP is highly expressed in hepatocellular carcinoma and associated with poor prognosis

Cited by 23 publications

References 38 publications

Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis

Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis

Expression of DIAPH1 is up‐regulated in colorectal cancer and its down‐regulation strongly reduces the metastatic capacity of colon carcinoma cells

Expression of Neural Wiskott-Aldrich Syndrome Protein in Clear Cell Renal Cell Carcinoma and Its Correlation with Clinicopathological Features

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