HOXB13 promotes ovarian cancer progression

Miao, Jiangyong; Wang, Zuncai; Provencher, Heather; Muir, Beth; Dahiya, Sonika; Carney, Erin; Leong, Chee Onn; Sgroi, Dennis; Oršulić, Sandra

doi:10.1073/pnas.0707938104

Cited by 105 publications

(101 citation statements)

References 34 publications

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“…To study the pathophysiological relevance of early events of the metastatic cascade in human tumors, we selected highly metastatic MDA MB-231 breast cancer and low metastatic OVCAR 8 ovarian cancer cell lines (23,24). Interestingly, implantation of MDA MB-231 breast cancer cells in zebrafish embryos resulted in widespread tumor cell dissemination and metastasis at day 6 post-injection ( Fig.…”

Section: Hypoxic Metastasis Model In Zebrafishmentioning

confidence: 99%

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model

Lee

Rouhi

Jensen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

225

188

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Mechanisms underlying pathological angiogenesis in relation to hypoxia in tumor invasion and metastasis remain elusive. Here, we have developed a zebrafish tumor model that allows us to study the role of pathological angiogenesis under normoxia and hypoxia in arbitrating early events of the metastatic cascade at the single cell level. Under normoxia, implantation of a murine T241 fibrosarcoma into the perivitelline cavity of developing embryos of transgenic fli1:EGFP zebrafish did not result in significant dissemination, invasion, and metastasis. In marked contrast, under hypoxia substantial tumor cells disseminated from primary sites, invaded into neighboring tissues, and metastasized to distal parts of the fish body. Similarly, expression of the hypoxia-regulated angiogenic factor, vascular endothelial growth factor (VEGF) to a high level resulted in tumor cell dissemination and metastasis, which correlated with increased tumor neovascularization. Inhibition of VEGF receptor signaling pathways by sunitinib or VEGFR2 morpholinos virtually completely ablated VEGFinduced tumor cell dissemination and metastasis. To the best of our knowledge, hypoxia-and VEGF-induced pathological angiogenesis in promoting tumor dissemination, invasion, and metastasis has not been described perviously at the single cell level. Our findings also shed light on molecular mechanisms of beneficial effects of clinically available anti-VEGF drugs for cancer therapy.hypoxia ͉ tumor invasion ͉ VEGF A ngiogenesis not only is essential for primary tumor growth but also facilitates tumor invasion and metastasis (1, 2). Tumor microvascular networks possess several unique pathological features distinguishing them from healthy blood vessels. These include extremely high densities of leaky, tortuous, and primitive microvessels that usually lack pericyte coverage, basement membrane, and arteriole-venule distinctions (3-6). These unusual features often create a hypoxic environment owning to poor blood perfusion, high interstitial fluid pressure (IFP), acidosis, and fast growth as well as metabolic rates of malignant tissues (7,8). Although hypoxia often results in necrosis of the central core of a fast-growing tumor, it could potentially persuade tumor cells to invade neighboring healthy vasculatures for survival, eventually leading to metastasis, which is one of the hallmarks for cancer therapy (9-13).Recent studies show that antiangiogenic drugs and vascular destructive agents also promote tumor cell invasion and metastasis in association with drug-induced tumor hypoxia (14-16). However, molecular mechanisms and detailed processes underlying hypoxiaassociated metastasis remain poorly understood. A clinical detectable metastatic mass often represents an ultimate consequence of several distinctive steps of the metastatic cascade, including dissemination of malignant cells from the primary site, transport of tumor cells via the circulation or lymphatic system, adhesion of tumor cells in distal tissues/organs, and re-growth of tumor cells into a detect...

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Section: Hypoxic Metastasis Model In Zebrafishmentioning

confidence: 99%

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model

Lee

Rouhi

Jensen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

225

188

View full text Add to dashboard Cite

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“…some tumors, aberrant Hox gene expressions directly drives tumorigenesis through escape from apoptosis [10], alterations to receptor signalling [11], tumor cell invasion [12], and epithelial-mesenchymal transition (EMT) [13].…”

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confidence: 99%

Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients

Zhang¹,

Jin²,

Yang³

et al. 2013

neo

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Human Hox genes (Homeobox) have crucial roles in development and differentiation, regulating numerous processes including apoptosis, receptor signalling, differentiation, motility and angiogenesis. Aberrant expression of Hoxc6 gene has been reported in several tumor tissues and cancer cell lines. The prognostic significance of Hoxc6 in gastric cancer remains largely unknown.This study was aimed to investigate the clinical significance of Hoxc6 in gastric cancer.Total RNA of paired tissue samples (n=25) and a tissue microarray containing 161 paired tissues from patients with gastric cancers at different stages were collected. Quantitative real-time PCR and immunochemistry assay were carried out to investigate the expression of Hoxc6.Hoxc6 mRNA was increased in gastric cancer tissues ( 16 of 25) compared with the adjacent normal mucosa (P<0.05). Immunohistochemical detection showed that expression of Hoxc6 was associated with the depth of tumor invasion (P<0.05). Patients with higher expression levels of Hoxc6 had a shorter overall survival rate (P<0.05).Hoxc6 might contribute to the progression of gastric carcinogenesis and may be a significant predictor of poor survival in patients with gastric cancer after curative operations.

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“…Most members of the HOX gene family are regarded as bidirectional regulation factors due to their tissue-specific expression and regulation (31). For example, HOXB13 was observed to be overexpressed in ovarian (32) and breast (33) cancer. Hwever, Jung et al (34) also reported that HOXB13 was downregulated in prostate cancer.…”

Section: No Of Patients Withmentioning

confidence: 99%

Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

Lai

et al. 2017

Oncol Lett

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Abstract. In a previous study by the present authors, it was identified that the expression of engrailed-2 (EN2) gene was downregulated in clear cell renal cell carcinoma (cc-RCC). The aim of the present study was to determine whether aberrant methylation was the mechanism underlying the silencing of EN2 gene in cc-RCC. A total of forty paired cc-RCC tissues, four cc-RCC cell lines and one normal human proximal tubule epithelial cell line were evaluated for EN2 gene methylation status using methylation-specific polymerase chain reaction (PCR). Following treatment with 5-Aza-dc, reverse transcription-quantitative PCR and western blot analysis were performed to examine the expression of EN2. Furthermore, cell proliferation, apoptosis and invasion assays were conducted to analyze the inhibitory effects of EN2 re-expression in 786-O cells. The results of the present study demonstrated that hyper-methylation of EN2 was identified in 12/40 cc-RCC tissues and all cc-RCC cell lines. The methylation status of the EN2 gene was revealed to be associated with histological grade and tumor size in cc-RCC. Following 5-Aza-dc treatment, demethylation of the EN2 gene was identified in 786-O cells, in conjunction with EN2 re-expression. Furthermore, re-activation of the EN2 gene markedly inhibited the proliferative and invasive capacities of cc-RCC. The results of the present study demonstrated that the EN2 gene promoter was hyper-methylated in cc-RCC, which may underlie the silencing of the EN2 gene in cc-RCC.

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HOXB13 promotes ovarian cancer progression

Cited by 105 publications

References 34 publications

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model

Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients

Engrailed‑2 promoter hyper‑methylation is associated with its downregulation in clear cell renal cell carcinoma

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