ASAP1 promotes tumor cell motility and invasiveness, stimulates metastasis formation in vivo, and correlates with poor survival in colorectal cancer patients

Müller, Torsten; Stein, Ulrike; Poletti, Anna; Garzia, Livia; Rothley, Melanie; Plaumann, Diana; Thiele, Wilko; Bauer, Matthew R.; Galasso, Alessia; Schlag, Peter M.; Pankratz, Michael J.; Zollo, Massimo; Sleeman, Jonathan

doi:10.1038/onc.2010.6

Cited by 90 publications

(96 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Arf6-ASAP1-EPB41L5 axis is another pathway to contribute to ASAP1-mediated EMT (18). ASAP1 was also shown to bind the SH3 domain of several members of the src family through its proline-rich domain and contributed to tumor metastasis in colorectal cancer (9). In addition, the non-coding endogenous small miRNAs also play a role in regulating EMT by directly targeting EMT marker genes or through indirect regulation.…”

Section: Discussionmentioning

confidence: 99%

“…ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) protein has N-terminal BAR, PH, ARF GAP, ankyrin repeat, proline-rich, and C-terminal SH3 domains (8). ASAP1 expression is upregulated in a variety of cancers as compared to normal tissue, and correlates with poor survival and prognosis in colorectal, and neck and head cancer patients (9,10). In breast cancer ASAP1expression contributes to tumor invasion and metastasis (11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

et al. 2018

View full text Add to dashboard Cite

Abstract. Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients. Lentiviral vector mediated ASAP1 expression promoted cell migration and invasion in ovarian cancer cell lines SKOV3 and OVCAR3. In addition, ASAP1 promoted cell proliferation, survival and inhibited chemotherapy drug paclitaxel-induced cell apoptosis. Furthermore, ASAP1 expression promoted epithelial to mesenchymal transition (EMT) by upregulating the mesenchymal cell markers N-cadherin and vimentin, and downregulating epithelial cell marker E-cadherin in the ovarian cancer cell lines. The data indicate for the first time that ASAP1 exhibits an oncogenic role by promoting EMT in ovarian cancer cells. IntroductionOvarian cancer is one of the most common gynecological malignancies with a high mortality rate (1). In 2017, 22,440 new cases and 14,080 deaths of ovarian cancer were estimated to occur in the United States (2). At the time of diagnosis, the majority of ovarian cancer patients have already progressed to advanced disease, due to the lack of early clinical symptoms, which results in high mortality (3). However, the molecular mechanisms underlying the tumor metastasis and chemoresistance in ovarian cancer are not well understood. The epithelial-mesenchymal transition (EMT) contributes to the tumor metastasis and chemoresistance (4). EMT is a biological process accompanied by the loss of cell adherence junctions and apical-basal polarity, and acquisition of the mesenchymal phenotype to increase cell motility and invasiveness (5). EMT marker gene expression is altered during the EMT process with downregulation of epithelial markers such as E-cadherin and upregulation of mesenchymal markers, including Snai1 and 2, N-cadherin, vimentin, Zeb 1/2, and Twist1/2 (6,7). ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) protein has N-terminal BAR, PH, ARF GAP, ankyrin repeat, proline-rich, and C-terminal SH3 domains (8). ASAP1 expression is upregulated in a variety of cancers as compared to normal tissue, and correlates with poor survival and prognosis in colorectal, and neck and head cancer patients (9,10). In breast cancer ASAP1expression contributes to tumor invasion and metastasis (11). ASAP1 is upregulated in ovarian cancer and associated with poor patient survival and prognosis (12). However, the function of ASAP1 in ovarian cancer has not been investigated.In the present study, we investigated the role of ASAP1 in ovarian cancer cells using lentiviral vector mediated overexpression. We demonstrated that ASAP1 was highly expressed in ovarian cancer and as...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…As revealed by the 2-DE data, the tubulin 5β spot had the highest-ranked change after Drosha-KD. Functionally, (24), Antiviral immunity and prevention of human hepatoma (25) inflammation (24) 4 Protein S100-A11 Lung cancer (26), Cell proliferation (26), a diagnostic marker breast carcinoma (27) in breast carcinoma (27) (48) stimulates metastasis formation (47,48) as an important component of the cytoskeleton, β-tubulin is associated with cell proliferation and the cell cycle and is a target of chemotherapeutic agents, such as paclitaxol.…”

Section: Drosha-kd Alters the Proteomic Profile Of Human Cervical Canmentioning

confidence: 99%

Proteomic identification of target proteins following Drosha knockdown in cervical cancer

et al. 2013

View full text Add to dashboard Cite

Abstract. The nuclear microRNA (miRNA) processing enzyme Drosha is upregulated in cervical cancer, and its overexpression is related to an invasive tumour phenotype. However, the mechanisms that underlie this effect remain poorly understood. The aim of this study was to identify the potential targets of Drosha in cervical cancer. Here, we demonstrated that Drosha knockdown (Drosha-KD) inhibited proliferation, colony formation and the migration of cervical cancer cells in vitro. A global upregulation of proteins in Drosha-KD cells was revealed by two-dimensional gel electrophoresis (2-DE). Eighteen proteins were identified by liquid chromatography and tandem mass spectrometry technology (LC-MS/MS) from 21 selected protein spots that exhibited significant alterations in Drosha-KD cells. The majority of the identified proteins have been previously associated with tumour formation. The downregulation of tubulin 5β in Drosha-KD cervical cancer cells was further confirmed by western blotting. Our results suggest that Drosha affects the biological activity of cervical cancer cells by regulating the expression of numerous tumourassociated proteins.

show abstract

“…The MicroPoly (A) Purist Kit (Ambion Inc.) was used according to manufacturer's instructions to isolate poly(A) mRNA. Customized in-house production of microarray chips as well as probe labeling and chip hybridization has been described previously (10). The arrays were scanned by using an Axon GenePix 4000B microarray scanner (Axon Instruments Inc.) and the GenePix Pro program.…”

Section: Microarray Analysis Mef/s100a4mentioning

confidence: 99%

Role of Fibulin-5 in Metastatic Organ Colonization

Møller

Ralfkjær

Cremers

et al. 2011

Molecular Cancer Research

View full text Add to dashboard Cite

The tumor microenvironment is now recognized as a major factor in determining the survival and growth of disseminated tumor cells at potential metastatic sites. Tumor cells send signals to stroma cells and stimulate them to produce factors that in turn create favorable conditions for tumor cell metastasis. Activated fibroblasts constitute an important component of the tumor-associated stroma. We have previously shown that S100A4 protein produced by stromal fibroblasts in the primary tumor stimulates metastasis formation. Here we show that activated fibroblasts also stimulate the formation of metastases independently of S100A4 expression during organ colonization. To identify genes that could potentially interfere with fibroblast-driven metastasis, we used gene expression profiling of S100A4-deficient fibroblasts treated with and without tumor cell-conditioned media. Five differentially expressed genes encoding cell surface and secreted proteins with potential metastasis-modulating activity were selected. Expression of lymphocyte antigen 6 complex (Ly6c) and matrix metalloproteinase 3 (Mmp3) was upregulated in fibroblasts in response to tumor-conditioned medium, whereas expression of cadherin-16 (Cdh16), Ccn2, and fibulin-5 (Fbln5) was downregulated. Further analysis showed that Fibulin-5 is able to suppress the metastatic colonization of lungs and liver. Additional studies suggest a mechanism in which Fibulin-5 suppresses metastasis formation by inhibiting production of matrix metalloproteinase 9 (MMP9) and reducing the invasive behavior of fibroblasts. Together our data are consistent with the notion that tumors secrete factors that downregulate expression of Fbln5 in fibroblasts at sites of metastatic colonization, in turn upregulating Mmp9 expression and stimulating metastatic organ colonization. Mol Cancer Res; 9(5); 553-63. Ó2011 AACR.

show abstract

ASAP1 promotes tumor cell motility and invasiveness, stimulates metastasis formation in vivo, and correlates with poor survival in colorectal cancer patients

Cited by 90 publications

References 34 publications

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

Proteomic identification of target proteins following Drosha knockdown in cervical cancer

Role of Fibulin-5 in Metastatic Organ Colonization

Contact Info

Product

Resources

About