WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

Yue, Zeng-Wen; Feng, Wenlong; Xiangke, L; Liuxing, W; Qingxia, F; Gao, Jianbo

doi:10.1038/cgt.2014.52

Cited by 12 publications

(14 citation statements)

References 25 publications

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“…Immunohistochemical (IHC) data showed that WASF3 is upregulated in high-grade breast tumors (10, 14). Similar analyses show the relationship between WASF3 expression levels and poor prognosis in non-small cell lung cancer (15), gastric cancer (16), hepatocellular carcinoma (17) and prostate cancer (11,18). Thus, analysis of WASF3 expression levels in primary cancers, are consonant with the in vitro studies showing WASF3 promotes cancer cell invasion.…”

Section: Introductionmentioning

confidence: 56%

The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis

et al. 2016

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Inactivation of the WASF3 gene suppresses invasion and metastasis of breast cancer cells. WASF3 function is regulated through a protein complex that includes the NCKAP1 and CYFIP1 proteins. Here we report that silencing NCKAP1 destabilizes the WASF3 complex, resulting in a suppression of the invasive capacity of breast, prostate and colon cancer cells. In an in vivo model of spontaneous metastasis in immunocompromized mice, loss of NCKAP1 also suppresses metastasis. Activation of the WASF protein complex occurs through interaction with RAC1, and inactivation of NCKAP1 prevents the association of RAC1 with the WASF3 complex. Thus, WASF3 depends on NCKAP1 to promote invasion and metastasis. Here we show that stapled peptides targeting the interface between NCKAP1 and CYFIP1 destabilize the WASF3 complex and suppress RAC1 binding, thereby suppressing invasion. Using a complex-disrupting compound identified in this study termed WANT3, our results offer a mechanistic proof of concept to target this interaction as a novel approach to inhibit breast cancer metastasis.

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Section: Introductionmentioning

confidence: 56%

The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis

et al. 2016

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“…WAVE3 is overexpressed in certain types of cancer, including ovarian cancer ( 6 ), breast cancer ( 7 ), prostate cancer ( 8 ), hepatocellular carcinoma ( 9 ), gastric cancer ( 10 ), and colorectal cancer ( 11 ). High expression levels of WAVE3 are associated with stronger capabilities for migration and invasion in some cancer types, and researchers have discovered that WAVE3 promotes the epithelial-mesenchymal transition (EMT) process to enhance the metastatic potential of certain types of cancer ( 10 , 12 ). Moreover, WAVE3 has also been shown to be associated with cell survival in certain types of cancer ( 6 , 8 , 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…High expression levels of WAVE3 are associated with stronger capabilities for migration and invasion in some cancer types, and researchers have discovered that WAVE3 promotes the epithelial-mesenchymal transition (EMT) process to enhance the metastatic potential of certain types of cancer ( 10 , 12 ). Moreover, WAVE3 has also been shown to be associated with cell survival in certain types of cancer ( 6 , 8 , 10 – 12 ). The mechanisms through which WAVE3 influences the biological properties of certain types of cancer have been examined in a few studies.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms through which WAVE3 influences the biological properties of certain types of cancer have been examined in a few studies. For example, WAVE3 has been shown to affect matrix metalloproteinases (MMPs), mitogen-activated protein kinase (MAPK) and Snail ( 6 , 8 , 10 , 11 , 13 ). Thus, WAVE3 enhances the proliferative, migratory and invasive abilities of cells in certain types of cancer, and similarities and differences exist in the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer

Huang

Chen

et al. 2018

Int J Oncol

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Alterations in Wiskott-Aldrich syndrome protein family verprolinhomologous protein 3 (WAVE3) expression play various roles in certain types of cancer. However, the roles of WAVE3 expression in pancreatic cancer remain unknown. The present retrospective study demonstrated that WAVE3 expression was higher in cancerous pancreatic tissues than in non-neoplastic tissues. Moreover, WAVE3 overexpression was related to lymphatic metastasis, a poor differentiation and high pre-operative CA19-9 levels and was an adverse prognostic factor for patients with pancreatic cancer. In vitro, the knockdown of WAVE3 inhibited the proliferative, migratory and invasive potential of pancreatic cancer cells and promoted cell apoptosis. Western blot analysis demonstrated that WAVE3 influenced the protein kinase B (PBK/AKT) pathway by suppressing the expression of pyruvate dehydrogenase kinase isoform 2 (PDK2) and then negatively inhibiting the phosphorylation of Ser473 on AKT. Furthermore, the expression of AKT pathway downstream proteins [certain epithelial-mesenchymal transition (EMT)-related proteins, p53, Bcl-2 and cyclin D1] was accordingly altered. Taken together, our findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway, and targeting WAVE3 and/or the AKT pathway may potentially serve as a treatment strategy for pancreatic cancer.

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“…Contrary to the postulated promigratory role of other actin-related proteins and NPFs, WAVE2 has been shown to be downregulated in gastric carcinoma, and, surprisingly, WAVE2 knockdown increased gastric carcinoma cell growth, invasiveness, motility, and adhesiveness and suppressed epithelial-mesenchymal transition in vitro [ 53 ]. Conversely, it has been reported that miRNA146a-induced downregulation of WAVE2 results in impaired migration and invasion, and WAVE3 expression enhances metastasis, invasion, and proliferation activity via upregulation of Snail in gastric cancer cell lines [ 54 , 55 ]. WAVE2 is strongly expressed in colorectal carcinoma cells, but only weakly in colonic epithelium maintaining normal structure; furthermore, colocalization of Arp2 and WAVE2 is associated with tumor cell budding, an established marker for aggressive tumor behavior in colorectal carcinoma and an independent risk factor for liver metastasis in CRC [ 30 , 56 ].…”

Section: Actin-related Proteins and Nucleation-promoting Factors Imentioning

confidence: 99%

Regulators of Actin Dynamics in Gastrointestinal Tract Tumors

Steinestel

Wardelmann

Hartmann

et al. 2015

Gastroenterology Research and Practice

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Reorganization of the actin cytoskeleton underlies cell migration in a wide variety of physiological and pathological processes, such as embryonic development, wound healing, and tumor cell invasion. It has been shown that actin assembly and disassembly are precisely regulated by intracellular signaling cascades that respond to changes in the cell microenvironment, ligand binding to surface receptors, or oncogenic transformation of the cell. Actin-nucleating and actin-depolymerizing (ANFs/ADFs) and nucleation-promoting factors (NPFs) regulate cytoskeletal dynamics at the leading edge of migrating cells, thereby modulating cell shape; these proteins facilitate cellular movement and mediate degradation of the surrounding extracellular matrix by secretion of lytic proteases, thus eliminating barriers for tumor cell invasion. Accordingly, expression and activity of these actin-binding proteins have been linked to enhanced metastasis and poor prognosis in a variety of malignancies. In this review, we will summarize what is known about expression patterns and the functional role of actin regulators in gastrointestinal tumors and evaluate first pharmacological approaches to prevent invasion and metastatic dissemination of malignant cells.

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WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

Cited by 12 publications

References 25 publications

The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis

The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis

WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer

Regulators of Actin Dynamics in Gastrointestinal Tract Tumors

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