Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis

Sinha, Pranav; Kohl, Sandra; Fischer, Jochen; Hütter, Gero; Kern, Manfred; Köttgen, Eckard; Dietel, Manfred; Lage, Hermann; Schnölzer, Martina; Schadendorf, Dirk

doi:10.1002/1522-2683(20000801)21:14<3048::aid-elps3048>3.0.co;2-w

Cited by 106 publications

(53 citation statements)

References 35 publications

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“…These studies demonstrated the importance of TCTP in maintaining genome stability under genotoxic stress, which is consistent with observations from Fujise's and our own laboratory, showing that TCTP is able to protect cancer cells against the cytotoxicity exerted by DNA-damaging anticancer drugs Bommer et al 2017). The involvement of TCTP in the development of chemoresistance in cancer chemotherapy has also been emphasised by several other papers (Jung et al 2014;Takahashi et al 2010;He et al 2015;Sinha et al 2000). 4.…”

Section: Involvement In Cellular Stress Responsessupporting

confidence: 86%

“…Sinha and co-workers performed a proteomics analysis on human melanoma cell lines that were resistant to drugs like vindesine, cisplatin and etoposide. They identified TCTP as one of four proteins overexpressed in those cell lines, compared to their no-resistant parental cells (Sinha et al 2000). Fujise's laboratory demonstrated TCTP (fortilin)-dependent drug resistance against etoposide (Li et al 2001) and 5-FU in U2OS cells.…”

Section: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 99%

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The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein. TCTP is able to interact with a large number of other proteins and is therefore involved in many core cell biological processes, predominantly in the response to cellular stresses, such as oxidative stress, heat shock, genotoxic stress, imbalance of ion metabolism as well as other conditions. Mechanistically, TCTP acts as an anti-apoptotic protein, and it is involved in DNA-damage repair and in cellular autophagy. Thus, broadly speaking, TCTP can be considered a cytoprotective protein. In addition, TCTP facilitates cell division through stabilising the mitotic spindle and cell growth through modulating growth signalling pathways and through its interaction with the proteosynthetic machinery of the cell. Due to its activities, both as an anti-apoptotic protein and in promoting cell growth and division, TCTP is also essential in the early development of both animals and plants. Apart from its involvement in various biological processes at the cellular level, TCTP can also act as an extracellular protein and as such has been involved in modulating whole-body defence processes, namely in the mammalian immune system. Extracellular TCTP, typically in its dimerised form, is able to induce the release of cytokines and other signalling molecules from various types of immune cells. There are also several examples, where TCTP was shown to be involved in antiviral/antibacterial defence in lower animals. In plants, the protein appears to have a protective effect against phytotoxic stresses, such as flooding, draught, too high or low temperature, salt stress or exposure to heavy metals. The finding for the latter stress condition is corroborated by earlier reports that TCTP levels are considerably up-regulated upon exposure of earthworms to high levels of heavy metals. Given the involvement of TCTP in many biological processes aimed at maintaining cellular or whole-body homeostasis, it is not surprising that dysregulation of TCTP levels may promote a range of disease processes, foremost cancer. Indeed a large body of evidence now supports a role of TCTP in at least the most predominant types of human cancers. Typically, this can be ascribed to both the anti-apoptotic activity of the protein and to its function in promoting cell growth and division. However, TCTP also appears to be involved in the later stages of cancer progression, such ...

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Section: Involvement In Cellular Stress Responsessupporting

confidence: 86%

Section: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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“…Elongation factor-1 delta may have other actions, such as effects on chemotherapy and ionising radiation (Jung et al, 1994;Sinha et al, 2000). Sinha et al (2000) indicated that human EF-1 delta was overexpressed in melanoma cell lines exhibiting chemoresistance towards antineoplastic drugs, such as vindesine, cisplatin, fotemstine and etoposide.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma

et al. 2004

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Elongation factor-1 (EF-1) delta is a subunit of EF-1, which is a protein complex that participates in the elongation step of mRNA translation and has recently been considered to correlate with oncogenic transformation. However, there has been no information regarding the clinical significance of EF-1 delta mRNA expression in malignant tumours, including oesophageal carcinoma. Thus, we quantitated the expression of EF-1 delta in malignant and benign oesophageal tissues and associated these levels with clinicopathologic parameters of oesophageal carcinoma. Paired oesophageal tissue samples from cancerous and corresponding noncancerous parts were obtained from 52 patients who underwent curative oesophagectomy. Quantitative analyses of EF-1 delta expression were performed using real-time quantitative reverse transcription -polymerase chain reaction. Elongation factor-1 delta mRNA overexpression in cancerous tissues compared to normal counterparts was observed in 38 of 52 (73%) patients. The mean expression level of EF-1 delta mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (Po0.01). A higher expression of EF-1 delta was significantly correlated with lymph node metastases (Po0.05) and advanced stages (Po0.05). Furthermore, the cause-specific survival of patients with a higher expression of EF-1 delta was significantly poorer than those with a lower expression (5-year cause-specific survival rates; 23 and 54%, respectively, Po0.05). The results of this study indicated that EF-1 delta mRNA expression was significantly higher in cancerous compared to noncancerous oesophageal tissues, and a higher expression of EF-1 delta mRNA was correlated with lymph node metastases, advanced disease stages and poorer prognosis for patients with oesophageal carcinoma.

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“…64 By analyzing global protein expression using 2-dimensional gel electrophoresis in drugsensitive and -resistant counterparts in human melanoma cell lines, various proteins have been detected and associated with the drugresistant phenotype. 65 For both approaches, further functional assays are needed to confirm the relevance of the identified molecules in conferring drug resistance in these cells. In light of the evidence gained so far, it appears that the lethality of malignant melanoma is due, to a large extent, to the ability of these tumor cells to resist chemotherapy; and any further knowledge gained on the nature of this resistance would improve the prospects of melanoma therapy.…”

Section: Conclusion and Future Perspectives In Research And Treatmentmentioning

confidence: 99%

Drug-resistance in human melanoma

Helmbach¹,

Rossmann²,

Kern³

et al. 2001

Int. J. Cancer

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165

137

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Advanced malignant melanoma has a poor prognosis since chemotherapy is mostly ineffective due in part to the intrinsic and/or extrinsic resistance of melanoma cells to systemic treatment with anti-neoplastic agents. The reasons for the chemoresistant phenotype are unknown. The relevance of well-analyzed drug-resistance mechanisms, e.g., intracellular/ extracellular transport and induction of certain enzyme systems, is reviewed. Most anti-cancer drugs kill susceptible cells through induction of apoptosis. Therefore, it appears that differences in the apoptotic pathways which lead to apoptotic deficiency may account for the ability of some tumor cells to resist drug therapy. Human melanomas, which are characteristically drug-resistant, are more likely to have altered apoptotic pathways and fewer pro-apoptotic molecules. Tumor cells with these characteristics are seldom sensitive to drugs. The complexity of the molecular variants involved in signal transduction along apoptotic pathways suggests that the cell may have a variety of possibilities for regulating apoptosis and generating apoptotic deficiency. Thus, apoptosis and apoptotic deficiency should be analyzed to better clarify the mechanisms of melanoma resistance.

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Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis

Cited by 106 publications

References 35 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma

Drug-resistance in human melanoma

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