Ephrin-A1 mRNA is associated with poor prognosis of colorectal cancer

Yamamoto, Hirofumi; Tei, Mitsuyoshi; Uemura, Mamoru; Takemasa, Ichiro; Uemura, Yoshio; Murata, Kohei; Fukunaga, Masao; Ohue, Masayuki; Ohnishi, Tadashi; Ikeda, Kimimasa; Kato, Takeshi; Okamura, Shu; Ikenaga, Masakazu; Haraguchi, Naotsugu; Nishimura, Junichi; Mizushima, Tsunekazu; Mimori, Koshi; Doki, Yuichiro; Mori, Masaki

doi:10.3892/ijo.2012.1750

Cited by 28 publications

(23 citation statements)

References 31 publications

(32 reference statements)

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“…In line with the results of the present study, hypoxic conditions are known to upregulate the expression of EFNA1 in hepatoma cells in vitro (34,35). We previously reported that silencing of EFNA1 in tumor cells inhibits the migration, invasion and proliferation of tumor cells themselves and also inhibits the migration of endothelial cells in coculture experiment (32). Thus, EFNA-mediated interactions between the endothelium and surrounding cells may be critical for vascular sprouting and the penetration of vessels into tumor tissues.…”

Section: Discussionsupporting

confidence: 77%

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

Wada

Yamamoto

Kim

et al. 2014

International Journal of Oncology

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Abstract. Hypoxia regulates the expression of genes that promote tumor growth, angiogenesis and invasion. We previously studied hypoxic tumor cells in vitro and from hepatic metastases of colorectal cancer and determined several potential prognostic factors for hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic impact of the expression of ephrin-A1 (EFNA1) and its receptor, EPHA2, in patients with HCC after curative resection. Samples from a total of 139 HCC patients were analyzed by either microarray alone (n=86) or by microarray and quantitative PCR (n=53). There was no correlation between EFNA1 expression and clinicopathological factors. EPHA2 expression was not significantly correlated with any clinicopathological factors, except for microscopic portal invasion. EFNA1 was an independent prognostic factor for HCC (p=0.0277). These findings suggest that EFNA1 expression may be a useful marker for predicting high risk of recurrence in patients who have undergone curative resection for HCC.

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Section: Discussionsupporting

confidence: 77%

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

Wada

Yamamoto

Kim

et al. 2014

International Journal of Oncology

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“…FGF-BP increases tumorigenicity and is highly expressed in colon carcinoma [64] TGM2 (transglutaminase 2) Elevated expression is found in compact spheroid formation by ovarian cancer cells [65] C. Transcripts down-regulated by resveratrol and up-regulated by IL-6 EFNA1 (Ephrin A1) It binds to the Eph A2 tyrosine kinase receptor, which drives migration and invasion of colorectal cancers. Its mRNA expression correlates with poor prognosis in hepatocarcinoma and colorectal cancers [41,66,67] THBS4 (thrombospondin 4) It is a stromal protein involved in cellular migration, adhesion, and attachment that has been shown to play a role in metastatic progression of lung, breast, and colorectal cancers [68][69][70] SGK1 (serum and glucocorticoid regulated Kinase 1)…”

Section: Il-6 and Resveratrol Modulate The Transcriptome And The Micrmentioning

confidence: 99%

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Ferraresi

Phadngam

Morani

et al. 2016

Molecular Carcinogenesis

102

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Interleukin-6 (IL-6), a pro-inflammatory cytokine released by cancer-associated fibroblasts, has been linked to the invasive and metastatic behavior of ovarian cancer cells. Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol and IL-6 affect in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells. Among the several potential candidates responsible for the anti-invasive effect promoted by Resveratrol, here we focused our attention on ARH-I (DIRAS3), that encodes a Ras homolog GTPase of 26-kDa. This protein is known to inhibit cell motility, and it has been shown to regulate autophagy by interacting with BECLIN 1. IL-6 down-regulated the expression of ARH-I and inhibited the formation of LC3-positive autophagic vacuoles, while promoting cell migration. On opposite, Resveratrol could counteract the IL-6 induction of cell migration in ovarian cancer cells through induction of autophagy in the cells at the migration front, which was paralleled by up-regulation of ARH-I and down-regulation of STAT3 expression. Spautin 1-mediated disruption of BECLIN 1-dependent autophagy abrogated the effects of Resveratrol, while promoting cell migration. The present data indicate that Resveratrol elicits its anti-tumor effect through epigenetic mechanisms and support its inclusion in the chemotherapy regimen for highly aggressive ovarian cancers. © 2016 Wiley Periodicals, Inc.

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“…We used this model to identify the following novel hypoxia-inducible genes: Jumonji domain containing 1A (JMJD1A) (12), adrenomedullin (ADM) (13), ephrin-A1 (EFNA1) (14), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) (15) and secretoglobin, family 2A, member 1 (SCGB2A1) (16).…”

Section: Fructose-bisphosphate Aldolase a Is A Key Regulator Of Hypoxmentioning

confidence: 99%

Fructose-bisphosphate aldolase A is a key regulator of hypoxic adaptation in colorectal cancer cells and involved in treatment resistance and poor prognosis

Kawai

Uemura

Munakata

et al. 2016

International Journal of Oncology

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Abstract.Hypoxia is an essential feature of cancer malignancy, but there are no methods for the routine detection of hypoxiainducible prognostic factors and potential therapeutic targets. We reported previously that the hypoxic tumor cells of metastatic liver tissue from patients with colorectal cancer (CRC) could be used as an 'in vivo' hypoxia culture model. Several potential hypoxia-inducible genes were identified using this model. Among them, one glycolytic enzyme was of special interest. There is currently increasing attention on glycolytic enzymes as potential therapeutic targets due to their association with cancer-specific metabolism. To better understand the molecular mechanisms of cancer malignancy, we investigated the expression of fructose-bisphosphate aldolase A (ALDOA) and its relationship with cancer metabolism. We found that ALDOA was induced by hypoxia in CRC-derived cell lines, and univariate and multivariate analyses of microarray data from the resected CRC samples of 222 patients revealed that ALDOA was an independent prognostic factor for CRC. We also analyzed the malignant potential of ALDOA in vitro using overexpression and knockdown assays. We found that ALDOA was negatively related to chemosensitivity and radiosensitivity and positively associated with proliferation, sphere formation and invasion in both normoxia and hypoxia. These associations were due to the roles of ALDOA in regulating glycolysis, the epithelial-mesenchymal transition and the cell cycle. These findings demonstrate that ALDOA is a hypoxiainducible prognostic factor that is closely related to CRC malignancy, and also provide new insights into the importance of ALDOA and glycolysis in cancer and suggest new targets for anticancer therapies.

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Ephrin-A1 mRNA is associated with poor prognosis of colorectal cancer

Cited by 28 publications

References 31 publications

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Fructose-bisphosphate aldolase A is a key regulator of hypoxic adaptation in colorectal cancer cells and involved in treatment resistance and poor prognosis

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