Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy

Kinoshita, Rumiko; Nam, Jwa Min; Ito, Yoichi M.; Hatanaka, Kanako C.; Hashimoto, Ari; Handa, Haruka; Otsuka, Yutaro; Hashimoto, Shigeru; Onodera, Yasuhito; Hosoda, Mitsuchika; Onodera, Shunsuke; Shimizu, Satoru; Tanaka, Shinya; Shirato, Hiroki; Tanino, Mishie; Sabe, Hisataka

doi:10.1371/journal.pone.0076791

Cited by 20 publications

(14 citation statements)

References 31 publications

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“…Our previous study, in which we examined the expression of AMAP1 and GEP100 by immunohistochemistry, demonstrated that co-overexpression of these 2 proteins exhibits a tight correlation with rapid local recurrence after breast conservative therapy, indicating that the ARF6-based pathway plays a central role in recurrence. 9 In accordance with this result, a recent report showed that the recurrence rates of breast cancer can be reduced by statins. 10 Other types of cancers, such as lung adenocarcinomas and head and neck squamous cell carcinomas, also overexpress the ARF6-based pathway (see refs.…”

supporting

confidence: 55%

Tumor responsiveness to statins requires overexpression of the ARF6 pathway

Sabe

Hashimoto

et al. 2016

Molecular & Cellular Oncology

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supporting

confidence: 55%

Tumor responsiveness to statins requires overexpression of the ARF6 pathway

Sabe

Hashimoto

et al. 2016

Molecular & Cellular Oncology

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“…40 An Arf6 pathway, which employs ASAP1 as its effector, activates b1 integrins and perturbs E-cadherin-based adhesion; hence it appears to be integral for EMT. 41 These results suggest that h-prune and its binding partner might be involved in activation of EMT.…”

Section: Discussionmentioning

confidence: 85%

“…Conversely, ASAP1 is a metastasis‐promoting factor that interacts with h‐prune and stimulates its phosphodiesterase activity, and it is associated with increased tumor cell motility and invasiveness in vitro . An Arf6 pathway, which employs ASAP1 as its effector, activates β1 integrins and perturbs E‐cadherin‐based adhesion; hence it appears to be integral for EMT . These results suggest that h‐prune and its binding partner might be involved in activation of EMT.…”

Section: Discussionmentioning

confidence: 95%

h‐Prune is associated with poor prognosis and epithelial–mesenchymal transition in patients with colorectal liver metastases

Hashimoto

Kobayashi

Tashiro

et al. 2016

Intl Journal of Cancer

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The prognosis of patients with colorectal liver metastases (CRLM) remains low despite advances in chemotherapy and surgery. The expression of h-prune (human homolog of Drosophila prune protein; HGNC13420), an exopolyphosphatase, is correlated with progression and aggressiveness in several cancers and promotes migration and invasion. We investigated the role of h-prune in CRLM. To investigate the role of h-prune, immunohistochemical analysis for h-prune was performed in 87 surgically resected specimens of CRLM obtained between 2001 and 2009 at the Hiroshima University Hospital. Immunohistochemical analysis revealed positive staining for h-prune in 24 (28%) cases. The overall survival rate was significantly lower in h-prunepositive cases than in h-prune-negative cases (p 5 0.003). Multivariate analysis showed that h-prune positivity was the only independent factor related to poor overall survival of patients after curative hepatectomy of CRLM. In vitro and in vivo, h-prune-knocked-down and h-prune-overexpressing cells were analyzed. In vitro, h-prune was associated with increased cell motility and upregulation of epithelial-mesenchymal transition (EMT) markers. In a mouse model, h-prune was associated with invasion of the tumor and distant metastases. In summary, h-prune expression is a useful marker to identify high-risk patients for resectable colorectal liver metastasis. h-Prune expression is necessary for cancer cell motility and EMT and is associated with liver and lung metastasis in colorectal cancer cells. h-Prune could be a new prognostic marker and molecular target for CRLM.Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide.1 Over 50% patients with CRC eventually develop liver metastases, and most patients who die of CRC have liver metastases.2 For patients with colorectal liver metastases (CRLM), surgical resection of the metastases remains the only curative treatment, despite advances in chemotherapy. However, the 5-year overall survival rate after hepatectomy is 40%.3,4 Therefore, there is an urgent need for new therapeutic modalities and molecular-targeted drugs for the treatment of CRLM.

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“…We showed that overexpression of ASAP1 promoted EMT in both SKOV3 and OVCAR3 cells, indicating that ASAP1 may contribute to tumor metastasis and chemoresistance in ovarian cancer cells. Although it is not clear how ASAP1 contributes to EMT in ovarian cancer cells, it was previously found that GEP100 activated an Arf6 pathway with ASAP1 serving as an effector via receptor tyrosine kinases (RTKs), thus activated beta1 integrins and disrupted E-cadherin-based adhesion and promoted EMT in breast cancer (17). Arf6-ASAP1-EPB41L5 axis is another pathway to contribute to ASAP1-mediated EMT (18).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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

Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy

Cited by 20 publications

References 31 publications

Tumor responsiveness to statins requires overexpression of the ARF6 pathway

Tumor responsiveness to statins requires overexpression of the ARF6 pathway

h‐Prune is associated with poor prognosis and epithelial–mesenchymal transition in patients with colorectal liver metastases

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

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