ARK5 is associated with the invasive and metastatic potential of human breast cancer cells

Chang, Xin; Yu, Jun; Liu, Hai Yin; Dong, Rui; Cao, Xu

doi:10.1007/s00432-011-1102-1

Cited by 41 publications

(44 citation statements)

References 19 publications

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“…It has three binding sites for miR-211 in its 3 0 UTR (Figure 4a). Functional studies revealed its involvement in induction of senescence (Humbert et al, 2010), regulation of proliferation through p53 phosphorylation (Hou et al, 2011), promotion of cell survival (Suzuki et al, 2003), invasion and metastasis Chang et al, 2012), and loss of cellular adhesion (Zagorska et al, 2010). Although NUAK1 is overexpressed in several cancers (Chang et al, 2012), little is known about its role in melanoma.…”

Section: Mir-211 Modulates Adhesion Ability Of Melanomasmentioning

confidence: 99%

Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Bell

Khaled

Netanely

et al. 2014

Journal of Investigative Dermatology

109

130

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Melanoma is one of the deadliest human cancers, responsible for approximately 80% of skin cancer mortalities. The aggressiveness of melanoma is due to its capacity to proliferate and rapidly invade surrounding tissues, leading to metastases. A recent model suggests melanoma progresses by reversibly switching between proliferation and invasion transcriptional signatures. Recent studies show that cancer cells are more sensitive to microRNA (miRNA) perturbation than are non-cancer cells; however, the roles of miRNAs in melanoma plasticity remain unexplored. Here, we use the gene expression profiles of melanoma and normal melanocytes to characterize the transcription factor-miRNA relationship that modulates the proliferative and invasive programs of melanoma. We identified two sets of miRNAs that likely regulate these programs. Interestingly, one of the miRNAs involved in melanoma invasion is miR-211, a known target of the master regulator microphthalmia-associated transcription factor (MITF). We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. Inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, whereas upregulation of miR-211 restores adhesion through NUAK1 repression. This study defines the MITF/miR-211 axis that inhibits the invasive program by blocking adhesion. Furthermore, we have identified NUAK1 as a potential target for the treatment of metastatic melanoma.

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Section: Mir-211 Modulates Adhesion Ability Of Melanomasmentioning

confidence: 99%

Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Bell

Khaled

Netanely

et al. 2014

Journal of Investigative Dermatology

109

130

View full text Add to dashboard Cite

show abstract

“…It suppresses cell death induced by nutrient starvation and activation of death receptors through inhibition of caspase 8, and the negative regulation of procaspase 6 (8,9). ARK5 is also strongly associated with tumor invasion and metastasis, and is a tumor survival and tumor progression factor (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer

Zhang

et al. 2015

Oncology Reports

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Epithelial ovarian cancer (EOC) is the sixth most common cancer in females worldwide and, although advances have been made in the detection, diagnosis and therapies for EOC, it remains the most lethal gynecologic malignancy in advanced countries. Nevertheless, relatively little is known concerning the molecular events that lead to the development of this highly aggressive disease. Elucidating the molecular mechanism involved in this disease may prove useful to understand the pathogenesis and progression of the disease, and to identify new targets for effective therapies. In the present study, we examined the role of ARK5 in ovarian cancer and normal matched tissues using western blot analysis and migration and invasion, and wound‑healing assays. The results showed that ARK5 was upregulated in ovarian cancer tissues, compared with adjacent normal tissues. Moreover, it promoted epithelial‑mesenchymal transition (EMT) and inhibited miR-1181 expression in ovarian cancer cells. Subsequent investigations showed that miR-1181 promoted mesenchymal-epithelial transition (MET) in ovarian cancer cells. Downstream target genes of miR-1181 were searched, and it was identified that miR-1181 degraded HOXA10 by targeting its 3' untranslated region (3'UTR) in ovarian cancer cells. The results confirmed that HOXA10 promoted EMT in ovarian cancer cells. Thus, activation of the ARK5/miR-1181/HOXA10 axis may be positively associated with EMT in ovarian cancer.

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“…NUAK1 has been shown to promote glioma cell invasion, and its elevated expression correlates with a poor clinical outcome (17). NUAK1 has also been shown to be associated with a more invasive phenotype and metastatic potential in human breast cancer dependent on Akt (18). In addition, the overexpression of NUAK1 is associated with a poor prognosis in hepatocellular carcinoma (19).…”

Section: Introductionmentioning

confidence: 99%

miR-96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer

Huang

Zhang

et al. 2014

International Journal of Molecular Medicine

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microRNA-96 (miR-96) is known to be downregulated in pancreatic cancer. The overexpression of miR-96 in MIA PaCa-2 pancreatic cancer cells has been shown to inhibit cell proliferation, migration and invasion; however, the mechanisms involved have not yet been fully elucidated. Novel (nua) kinase family 1 (NUAK1) functions as an oncogene in non‑small cell lung cancer (NSCLC), melanoma, glioma, breast cancer, hepatocellular carcinoma and pancreatic cancer. In this study, firstly, we demonstrate that NUAK1 expression is specifically upregulated in pancreatic cancer and that it promotes the proliferation, migration and invasion of MIA PaCa-2 pancreatic cancer cells. Secondly, we performed an analysis of potential microRNA (miRNA) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-96 targets the 3' untranslated region (3' UTR) of NUAK1. Further experiments confirmed this prediction, namely that miR-96 suppresses the expression of NUAK1 by targeting its 3' UTR. Finally, we demonstrate that the introduction of NUAK1 cDNA lacking predicted sites of the 3' UTR abrogates miR-96 cellular function.

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ARK5 is associated with the invasive and metastatic potential of human breast cancer cells

Abstract: ARK5 led to a more invasive phenotype and metastatic potential in human breast cancer dependent on Akt.

Cited by 41 publications

References 19 publications

Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer

miR-96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer

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