Decreased GRP78 Protein Expression is a Potential Prognostic Marker of Oral Squamous Cell Carcinoma in Taiwan

Huang, Tze Ta; Chen, Jeff Yi Fu; Tseng, Chih En; Su, Yu Chieh; Ho, Han‐Chen; Lee, Moon Sing; Chang, Chiou Tuz; Wong, Yong–Kie; Chen, Hau Ren

doi:10.1016/s0929-6646(10)60060-5

Cited by 38 publications

(37 citation statements)

References 21 publications

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“…The OCSL cells showed greater proliferation, horizontal and vertical migration, and transwell invasion abilities in comparison with OC2 cells [32]. In this study, we demonstrated that reversine suppressed the growth of these two OSCC cells.…”

Section: Discussionmentioning

confidence: 54%

“…Especially, the apoptosis percentage was over fifty in OCSL cells after 24 hours treatment. (Figure 3B), highly suggesting that reversine was more effective in OCSL cells, the cell line previously proven more malignant than OC2 [32]. …”

Section: Resultsmentioning

confidence: 85%

“…To evaluate the potential effect of reversine on suppressing OSCC cell growth, two cell lines OCSL and OC2 cells established from the local patients were examined [32]. The endogenous levels of phosphorylated aurora kinases were detectable, implying the potential application of reversine for suppressing the growth of oral cancer cells (Additional file 1A).…”

Section: Resultsmentioning

confidence: 99%

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Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy

Lee

et al. 2012

J Biomed Sci

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BackgroundThe effective therapies for oral cancer patients of stage III and IV are generally surgical excision and radiation combined with adjuvant chemotherapy using 5-Fu and Cisplatin. However, the five-year survival rate is still less than 30% in Taiwan. Therefore, evaluation of effective drugs for oral cancer treatment is an important issue. Many studies indicated that aurora kinases (A, B and C) were potential targets for cancer therapies. Reversine was proved to be a novel aurora kinases inhibitor with lower toxicity recently. In this study, the potentiality for reversine as an anticancer agent in oral squamous cell carcinoma (OSCC) was evaluated.MethodsEffects of reversine on cell growth, cell cycle progress, apoptosis, and autophagy were evaluated mainly by cell counting, flow cytometry, immunoblot, and immunofluorescence.ResultsThe results demonstrated that reversine significantly suppressed the proliferation of two OSCC cell lines (OC2 and OCSL) and markedly rendered cell cycle arrest at G2/M stage. Reversine also induced cell death via both caspase-dependent and -independent apoptosis. In addition, reversine could inhibit Akt/mTORC1 signaling pathway, accounting for its ability to induce autophagy.ConclusionsTaken together, reversine suppresses growth of OSCC via multiple mechanisms, which may be a unique advantage for developing novel therapeutic regimens for treatment of oral cancer in the future.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

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Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy

Lee

et al. 2012

J Biomed Sci

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“…Fadu, a hypopharynx squamous cell carcinoma cell line, and 2 oral cancer cell lines, OC2 and OCSL, two oral squamous cell carcinoma cell lines derived from two Taiwanese men with habits of drinking, smoking, and areca nut chewing [33], were maintained in RPMI medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. The oral cancer cell lines SCC4 and SCC25, two tongue squamous cell carcinoma cell lines, were maintained in DMEM/F12 with similar supplements.…”

Section: Methodsmentioning

confidence: 99%

Monocyte Chemotactic Protein 1 (MCP-1) Modulates Pro-Survival Signaling to Promote Progression of Head and Neck Squamous Cell Carcinoma

Chen

Lin

et al. 2014

PLoS ONE

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BackgroundMonocyte chemotactic protein-1 (MCP-1) recruits monocytes and macrophages to inflammation sites, and inflammatory infiltration correlates with the progression of head and neck squamous cell carcinoma (HNSCC). This study aims to determine whether MCP-1 expression is related to HNSCC malignancy and patient survival. We also investigated the relationship between MCP-1 expression and the phosphorylation state of the pro-survival pathway factors Akt, ERK, and STAT3.MethodsExpression of MCP-1 and related proteins in HNSCC cell lines was investigated using western blotting. HNSCC patients (34) without distant metastasis at diagnosis were recruited for tissue specimen evaluation of MCP-1 expression and clinical outcomes. The relationship between MCP-1 expression and survival was evaluated using the Cox proportional hazard model with stepwise selection.ResultsHigh-grade HNSCC cell lines were found to have higher levels of active Akt, ERK, and/or STAT3 than did lower grade cell lines under serum-free condition. OCSL, the most malignant cell line, had the highest level of endogenous MCP-1. Administration of exogenous recombinant MCP-1 increased phosphorylation of Akt, ERK, and STAT3 in a dose- and time-dependent manner and increased cellular resistance to serum starvation. Inhibition of Akt, ERK, or STAT3 reduced cell growth and caused cell death. Long-term survival of HNSCC patients was negatively associated with the histological intensity of MCP-1, implicating MCP-1 as a potential prognostic marker for HNSCC.ConclusionsThese results suggest that overexpressed MCP-1 in cancer cells may promote HNSCC progression through upregulating pro-survival signaling pathways. High cellular MCP-1 expression is related to poor overall survival rate in HNSCC patients.

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“…99 GRP78 is overexpressed in 76% of breast cancers, and in lung, gastric and hepato cellular tumors, but downregulated in oral squamous-cell cancers. [100][101][102][103][104] In addition to its role within the endo plasmic reticulum, GRP78 has been found on the surface of prostate cancer cells. 105 Although the exact role of GRP78 in cancer cells remains elusive, it prevents apoptosis by binding and inhibiting caspase 7 and suppressing the pro apoptotic proteins BIK and BAX and mitochondrial release of cytochrome c. 106,107 Introduction of GRP78 confers drug resistance in cancer cells, which are resensitized to cytotoxic chemotherapy when it is removed.…”

Section: Deregulated Global Control and Cancermentioning

confidence: 99%

The biological and therapeutic relevance of mRNA translation in cancer

2011

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Protein synthesis is a tightly regulated process that enables post-transcriptional control of gene expression. Dysregulation of this process is associated with the development and progression of cancers because components of the translational machinery function at the point of convergence of aberrant cell signaling pathways. Drugs designed to inhibit mRNA translation are currently in preclinical and early clinical development, and are likely to provide effective anticancer strategies in the future. In this Review, we summarize the main components of translation and describe how alterations in these proteins and their principle upstream signaling pathways can impact on cancer. The first inhibitors of translation, drugs designed to target eIF4E, have been trialed in hematologic malignancies, while antisense oligonucleotides against eIF4E are also due to enter clinical trials. Here, we discuss the mode of action of drugs designed to inhibit mRNA translation and other promising therapies that are in preclinical development with the aim of becoming anticancer agents.

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Decreased GRP78 Protein Expression is a Potential Prognostic Marker of Oral Squamous Cell Carcinoma in Taiwan

Abstract: GRP78 protein is a possible biomarker of oral cancer in Taiwan.

Cited by 38 publications

References 21 publications

Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy

Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy

Monocyte Chemotactic Protein 1 (MCP-1) Modulates Pro-Survival Signaling to Promote Progression of Head and Neck Squamous Cell Carcinoma

The biological and therapeutic relevance of mRNA translation in cancer

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