Dataset Information

Overexpression of ?-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

ABSTRACT: Abnormal expression of ?-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of ?-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of ?-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with ?-catenin knockin and knockdown. In this study, we found that higher expression level of ?-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of ?-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of ?-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of ?-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of ?-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3?, C-myc, Bcl-2, P-gp, and MRP-1 were involved in ?-catenin-mediated drug resistance. Our findings indicate that the Wnt/?-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.

SUBMITTER: Li L

PROVIDER: S-EPMC4978817 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Overexpression of β-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Li Long L Liu Hai-Chao HC Wang Cheng C Liu Xiqiang X Hu Feng-Chun FC Xie Nan N Lü Lanhai L Chen Xiaohua X Huang Hong-Zhang HZ

BioMed research international 20160727

Abnormal expression of β-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of β-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of β-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with β-catenin knockin and knockdown. In this study, we found that higher expr ...[more]

PMID: 27529071

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Project description:BackgroundFascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.MethodsTo understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.ResultsFascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients.ConclusionIn conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.

Dataset Information

Overexpression of ?-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Publications

Overexpression of β-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

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