Plasminogen activator inhibitor‐1 as regulator of tumor‐initiating cell properties in head and neck cancers

Lee, Jong-Kang; Yu, Cheng–Chia; Lan, Chih; Lee, Che‐Hsin; Lee, Hsueh-Te; Kuo, Yu‐Liang; Wang, Po-Hui; Chang, Wen‐Wei

doi:10.1002/hed.24124

Cited by 21 publications

(22 citation statements)

References 53 publications

(97 reference statements)

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“…We previously discovered that the overexpression of miR-494-3p in aldehyde dehydrogenase 1 (ALDH1)+ CD44+ HNC-TICs inhibited their cancer stemness [ 13 ]. Given that radioresistance is one of the properties of HNC-TICs [ 15 ], the correlation between radiation response and miR-494-3p expression was examined first. As shown in Figure 1 , the expression of miR-494-3p displayed a negative correlation with cell survival after radiation in SAS cells ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

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miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

Weng

Lee

et al. 2016

IJMS

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Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18–25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16INK4a and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1.

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Section: Resultsmentioning

confidence: 99%

“…Previous studies reported that HNC-TICs displayed a radioresistant feature [ 14 , 15 ]. The present study further examined the function of miR-494-3p and its target gene Bmi1 in the radiation response of the SAS OSCC cell line.…”

Section: Introductionmentioning

confidence: 99%

miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

Weng

Lee

et al. 2016

IJMS

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“…Many targets for pharmaceutical intervention to prevent fibrosis and cardiovascular morbidity after irradiation have been investigated, for example, blocking the renin-angiotensin-aldosterone system through angiotensin-converting enzyme inhibitors and angiotensin receptor blockers or by using statins [ 29 – 34 ]. Tiplaxtinin (PAI-039, a PAI-1-inhibitor) is an interesting pharmacological agent that has been shown to reduce self-renewal and resistance to radiation in tumor-initiating cells in HNSCC [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Plasminogen Activator Inhibitor-1 in Irradiated Recipient Arteries and Veins from Free Tissue Transfer Reconstruction in Cancer Patients

Eriksson

Gahm

Halle

2018

Mediators of Inflammation

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Background Clinical studies have shown that radiotherapy can induce vascular disease at the site of exposure but is usually not clinically evident until years after treatment. We have studied irradiated human arteries and veins to better understand the underlying biology in search of future treatments. The aim was to investigate whether radiotherapy contributed to a sustained expression of plasminogen activator inhibitor-1 (PAI-1) in human arteries and veins. Methods Irradiated arteries and veins were harvested, together with unirradiated control vessels, from patients undergoing free tissue transfer reconstruction at a median time of 90 weeks [5–650] following radiation exposure. Differential gene expression of PAI-1 was analysed, together with immunohistochemistry (IHC) and immunofluorescence (IF). Results PAI-1 gene expression was increased in both arteries (p = 0.012) and veins (p < 0.001) in irradiated compared to unirradiated control vessels. IHC and IF indicated that cells expressing PAI-1 were located in the adventitia of both arteries and veins and colocalized with cells positive for CD68, CD45, and α-SMA in arteries and with CD45 and α-SMA in veins. Conclusion The current study shows a sustained upregulation of PAI-1 in both arteries and veins after exposure to ionizing radiation, indicating a chronic inflammation mainly in the adventitia. We believe that the results contribute to further understanding of radiation-induced vascular disease, where targeting PAI-1 may be a potential treatment.

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“…Nevertheless, substantial studies suggest that PAI-1 at pharmacological levels hinders cancer growth and angiogenesis [123,128,130,131,134-137]. The suppression of PAI-1 by Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, or siRNA can inhibit tumor-initiating cells within head and neck cancer cell lines via downregulating the sex-determining region Y-box 2 (Sox2) [138]. Some studies reveal that antibodies against PAI-1 may inhibit human cancer cell metastasis in mouse xenograft models [139-141].…”

Section: Plasminogen Activator Inhibitor-1 (Pai-1)mentioning

confidence: 99%

Diabetes-associated dysregulated cytokines and cancer

Wu¹,

Liu²,

Dong³

et al. 2016

Integr Cancer Sci Therap

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Epidemiological data demonstrate that patients with diabetes have an augmented risk of developing various types of cancers, accompanied by higher mortality. A number of mechanisms for this connection have been hypothesized, such as insulin resistance, hyperinsulinemia, hyperglycemia, and increased inflammatory processes. Apart from these potential mechanisms, several diabetes-associated dysregulated cytokines might be implicated in the link between diabetes and cancer. In fact, some inflammatory cytokines, e.g. TNF-α, IL-6 and leptin, have been revealed to play important roles in both initiation and progression of tumor. Here, we depict the role of these cytokines in key events of carcinogenesis and cancer development, including their capability to induce oxidative stress, inflammation, their participation in epithelial mesenchymal transition (EMT), angiogenesis, and metastasis. Finally, we will also highlight the existing knowledge in terms of the involvement of these cytokines in different cancer types and comment on potential significances for future clinical applications.

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Plasminogen activator inhibitor‐1 as regulator of tumor‐initiating cell properties in head and neck cancers

Abstract: The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2. © 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904, 2016.

Cited by 21 publications

References 53 publications

miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

Upregulation of Plasminogen Activator Inhibitor-1 in Irradiated Recipient Arteries and Veins from Free Tissue Transfer Reconstruction in Cancer Patients

Diabetes-associated dysregulated cytokines and cancer

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