The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies

Su, Shih‐Chi; Lin, Chiao‐Wen; Yang, Wei‐En; Fan, Wen‐Lang

doi:10.1517/14728222.2016.1113260

Cited by 128 publications

(113 citation statements)

References 161 publications

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“…Cancer is the result of a series of genetic or epigenetic regulations, and environmental risk factors may contribute to the development and progression of tumors [21, 43]. Thus, in-depth understanding of the mechanisms underlying carcinogenesis is needed to characterize genetic alterations linked to OSCC development [44].…”

Section: Discussionmentioning

confidence: 99%

A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma

et al. 2017

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Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3’-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.

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Section: Discussionmentioning

confidence: 99%

A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma

et al. 2017

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“…During the progress of a metastasis, it is critical that cancers cells secrete the proteases for digesting ECM and allow themselves to migrate to other tissues or organs . Previous studies have revealed that two MMPs (MMP‐2 and MMP‐9) are highly expressed in various types of malignant tumors .…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of Leucaena leucocephala on the metastasis and invasion of human oral cancer cells

Chung

Chen

Chang

et al. 2017

Environmental Toxicology

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Oral cancer is one of the most common cancers worldwide, and metastasis is recognized as a major factor causing its low survival rate. The inhibition of metastasis progress and the improvement of the survival rate for oral cancer are critical research objectives. Leucaena leucocephala from the mimosa branch Leucaena genus is native to Central and South America and has been used as a traditional remedy for treating various disorders. Previous studies have demonstrated antioxidant, anti-inflammatory as well as anticancer properties of L. leucocephala plant materials. However, the molecular mechanism underlying the anticancer effect induced by L. leucocephala remains unclear. In this study, we investigated the effect of L. leucocephala extract (LLE) on SCC-9 and SAS oral cancer cells and examined the potential inhibitory mechanisms involved. The results indicated that LLE attenuated the migration and invasion abilities of both SCC-9 and SAS cells by reducing the activity and protein expression of matrix metalloproteinases-2 (MMP-2). Regarding mitogen-activated protein kinase (MAPK) pathways, the phosphorylation of ERK1/2 and p38 exhibited a significant inhibitory effect in the presence of LLE. The application of ERK inhibitor and p38 inhibitor confirmed that both signalling transduction pathways were involved in the inhibition of cell metastasis. These data indicate that L. leucocephala could be a potent therapeutic agent for the prevention and treatment of oral cancer and a prominent plant source for anticancer research in the future.

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“…The proteolytic events of the metastasis process involve various proteases, such as serine proteinase, plasminogen activator, cathepsin and matrix metalloproteinases (MMPs) (Cheng et al, 2016;Su et al, 2016;Yeh et al, 2016;Su et al, 2017). MMPs are a family of zinc-dependent endopeptidases that are collectively capable of degrading most components of the basement membrane and ECM, and increased expressions of these enzymes are detected in almost all human cancers and have been associated with the aggressiveness of various neoplasms (Cox et al, 2001;Shuman Moss et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

et al. 2017

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Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by The American Journal of Chinese Medicine, Vol. 45, No. 7, 1557-1572© 2017 down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

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The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies

Cited by 128 publications

References 161 publications

A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma

A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma

Inhibitory effects of Leucaena leucocephala on the metastasis and invasion of human oral cancer cells

Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

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