Human Leucine Zipper Protein sLZIP Induces Migration and Invasion of Cervical Cancer Cells via Expression of Matrix Metalloproteinase-9

Kang, Hee-Jun; Jang, Su-Jin; Ko, Jesang

doi:10.1074/jbc.m111.272302

Cited by 30 publications

(23 citation statements)

References 38 publications

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“…They are involved in the degradation of the extracellular matrix (ECM) and play a role in the invasion and metastasis of tumor cells (3,4). Previous studies (36)(37)(38) have suggested that disruption to the ECM during tumor progression is due to an imbalance in the MMP/TIMP ratio. Our study revealed that a significant upregulation of MMP-9 and TIMP-1 protein expression in JEG-3 cells was observed following treatment with TGF-β1 at concentrations of 100 and 200 µg/l.…”

Section: Discussionmentioning

confidence: 99%

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

Zhang

et al. 2012

Oncology Letters

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Abstract. Human choriocarcinoma is one of the most aggressive malignant tumors characterized by early hematogenous spread to lung and brain tissues, and may be a cause of death in patients. Choriocarcinoma may occur following pregnancy and during implantation; however, trophoblastic invasion in human pregnancy is tightly regulated. The transforming growth factor-beta 1 (TGF-β1) has been suggested to play a role in controlling this process. In this study, we investigated the impact of TGF-β1 on invasion, as well as its sites of action in the TGF-β1/Smad pathway using a JEG-3 choriocarcinoma cell line. Following the treatment of cells with different doses of TGF-β1, cell invasion was observed. We also detected the expression of TGF-β receptor type I (TβR I) and TGF-β receptor type II (TβR II), Smad4, matrix metalloprotease (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in JEG-3 cells. Our data demonstrated that TGF-β1 promoted the invasive capability of JEG-3 cells depending on the downregulation of TβR I, TβR II, Smad4 and the upregulation of MMP-9 and TIMP-1. These observations suggest that TGF-β1 may play a critical role in the initiation of the trophoblastic invasion process. IntroductionA successful human pregnancy requires embryonic trophocytes to invade into the womb and adhere to the endometrium; however, this kind of invasion is strictly regulated temporospatially (1). The deregulation of the invasion process may cause a series of pregnancy-related diseases, such as hydatidiform mole and invasive mole; however, excessive invasion of trophocytes is significantly associated with the formation of placental choriocarcinoma (2). In this process, one critical step of choriocarcinoma invasion and metastasis is the degradation of the extracellular matrix (ECM), in which the MMP-9/TIMP-1 ratio plays a significant role (3,4).The main treatment for choriocarcinoma is 5-fluorouracil, which has a very good therapeutic efficacy; however, it may also cause toxic reactions, side effects and drug resistance (5). Since conventional treatments including surgery and chemotherapy often fail, it is necessary to explore the metastasis mechanisms of proliferation and invasiveness, and find a new target for drug therapy.TGF-β belongs to a growth factor super-family which consists of a highly evolutionary conserved group of secreted cytokines (6). The TGF-β family consists of TGF-β, activins, bone morphogenetic proteins (BMPs), nodals, inhibins and antimullerian hormone (AMH). TGF-β1 is the prototypic family member and is secreted as an inactive latent precursor (7,8). It plays a significant role in the control of growth and development, including the regulation of cell proliferation and differentiation, the promotion of ECM formation and suppression of the immune response (9). TGF-β1 exerts its cellular effects through TβR I, TβR II and the Smad transcription factors, which have pivotal roles in intracellular signaling (7,10). Moreover, Smad4 is an essential factor in TGF-β signaling and is a frequently mutated tumor ...

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Section: Discussionmentioning

confidence: 99%

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

Zhang

et al. 2012

Oncology Letters

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“…sLZIP negatively regulates transactivation of the glucocorticoid receptor via recruitment of histone deacetylases (HDACs) to the glucocorticoid response element of target genes, leading to suppression of glucocorticoid receptor-mediated gene expression (1). sLZIP is involved in activation of matrix metalloproteinase (MMP)-9 transcription via direct binding to the cAMP-responsive element of the MMP-9 promoter, resulting in an increase in cell migration and invasion in cervical cancer cells (2). sLZIP also promotes phorbol 12-myristate 13-acetate-induced breast cancer cell migration via up-regulation of ADP-ribosylation factor 4 expression (3).…”

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confidence: 99%

“…The small leucine zipper protein (sLZIP), 2 a novel isoform of human LZIP, is located in the nucleus and functions as a transcription cofactor (1). sLZIP negatively regulates transactivation of the glucocorticoid receptor via recruitment of histone deacetylases (HDACs) to the glucocorticoid response element of target genes, leading to suppression of glucocorticoid receptor-mediated gene expression (1).…”

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confidence: 99%

Small Leucine Zipper Protein (sLZIP) Negatively Regulates Skeletal Muscle Differentiation via Interaction with α-Actinin-4

Kim

Yoo

et al. 2014

Journal of Biological Chemistry

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Background: Cooperation between transcription factors and myogenic regulatory factors is important for skeletal muscle differentiation. Results: sLZIP inhibits expression of muscle-specific genes during myogenesis via disruption of an association between ␣-actinin-4 and MEF2. Conclusion: A novel myogenesis regulatory mechanism of sLZIP is characterized. Significance: sLZIP can be used as a therapeutic target for treatment of muscle diseases.

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“…13,14 Our results showed an association of high LUZP expression with more aggressive tumor behavior, including higher a-FP level, advanced TNM stage, and higher recurrence incidence. High a-FP level and advanced TNM stage are clinicopathologic markers of invasiveness and unfavorable prognosis in patients with HCC.…”

mentioning

confidence: 75%

“…Abnormal expression of LUZP protein is found in many types of tumor such as breast cancer, kidney cancer, cervical cancer, and pancreatic cancer. [11][12][13][14] In this study, we examined expression of LUZP messenger RNA (LUZP mRNA) in tumor versus adjacent noncancerous liver tissues in 77 patients with HCC who received surgical resection. Potential correlations of expression of LUZP mRNA with clinicopathological characteristics of HCC (eg, TNM staging and survival) were also analyzed.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Leucine Zipper Protein mRNA in Hepatocellular Carcinoma Associated With Poor Prognosis

Liu

et al. 2015

Technol Cancer Res Treat

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Background: Leucine zipper protein (LUZP) plays key roles in development. Overexpression of LUZP was documented in several types of solid tumors. In this study, expression of LUZP messenger RNA (LUZP mRNA) in human hepatocellular carcinoma (HCC) was examined, and the correlations of LUZP mRNA level with patients' characteristics and prognosis were also investigated. Methods: Total RNA was extracted from HCC and paired noncancerous liver tissues of 77 patients. Expression of LUZP mRNA in the tissues was determined by real-time quantitative reverse transcriptase polymerase chain reaction. Using average LUZP mRNA level in noncancerous liver tissues as the cutoff, patients with HCC were categorized into high-expression group and low-expression group. Correlations of LUZP mRNA with clinical parameters were analyzed. Overall survival of the patients in the 2 groups was analyzed by Kaplan-Meier method. Results: The LUZP mRNA level was significantly higher in HCC samples than in the noncancerous liver tissues (1.87 + 0.11 vs 0.58 + 0.05, P < .01). Significant differences were found between the 2 groups in terms of portal vein invasion, Tumor Lymph Node Metastasis (TNM) stage, and recurrence of HCC. The current study failed to find significant differences between the 2 groups in clinical characteristics such as age, gender, lymph node metastasis, hepatitis B virus infection, family HCC history, and alcohol intake. Overall survival in high-expression group was 12 months while that in the lowexpression group was 34 months (P ¼ .03). Conclusion: The LUZP mRNA is a prognostic indicator in HCC, and overexpression is associated with poor prognosis in patients with HCC.

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Human Leucine Zipper Protein sLZIP Induces Migration and Invasion of Cervical Cancer Cells via Expression of Matrix Metalloproteinase-9

Cited by 30 publications

References 38 publications

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

Small Leucine Zipper Protein (sLZIP) Negatively Regulates Skeletal Muscle Differentiation via Interaction with α-Actinin-4

Upregulation of Leucine Zipper Protein mRNA in Hepatocellular Carcinoma Associated With Poor Prognosis

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