Allogenic antibody-mediated identification of head and neck cancer antigens

Rauch, Jens; Ahlemann, Martin; Schaffrik, Martina; Mack, Brigitte; Ertongur, Suna; Andratschke, Michaela; Zeidler, Reinhard; Lang, Stephan; Gires, Olivier

doi:10.1016/j.bbrc.2004.08.071

Cited by 64 publications

(39 citation statements)

References 27 publications

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“…hnRNP A2 regulates the splicing of A-Raf reducing the production of a dominant-negative A-Raf isoform Elevated A-Raf expression levels have been observed in a number of malignancies, including astrocytomas (Hagemann et al 2009), pancreatic ductal carcinoma (Kisanuki et al 2005), angioimmunoblastic lymphadenopathies (Mark et al 1986), head and neck squamous cell carcinomas, and colon carcinomas (Rauch et al 2004(Rauch et al , 2010. A recent study reported that A-Raf undergoes alternative splicing generating a short isoform which has a dominant-negative effect on A-Raf ( Fig.…”

Section: Hnrnp A2 Activates the Ras-mapk-erk Pathwaymentioning

confidence: 99%

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Shilo¹,

Hur²,

Denichenko³

et al. 2014

RNA

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In recent years, it has become clear that splicing factors play a direct role in cancer development. We showed previously that splicing factors SRSF1, SRSF6, and hnRNP A2/B1 are up-regulated in several cancers and can act as oncogenes when up-regulated. Here we examined the role of splicing factors hnRNP A1/A1b and hnRNP A2/B1 in hepatocellular carcinoma (HCC). We show that the splicing factors hnRNP A1 and hnRNP A2 are up-regulated in HCC tumors derived from inflammation-induced liver cancer mouse model. Overexpression of hnRNP A1 or hnRNP A2, but not the splicing isoform hnRNP B1, induced tumor formation of immortalized liver progenitor cells, while knockdown of these proteins inhibited anchorage-independent growth and tumor growth of human liver cancer cell lines. In addition, we found that cells overexpressing hnRNP A2 showed constitutive activation of the Ras-MAPK-ERK pathway. In contrast, knockdown of hnRNP A2 inhibited the Ras-MAPK-ERK pathway and prevented ERK1/2 activation by EGF. Moreover, we found that hnRNP A2 regulates the splicing of A-Raf, reducing the production of a short dominant-negative isoform of A-Raf and elevating the full-length A-Raf transcript. Taken together, our data suggest that hnRNP A2 up-regulation in HCC induces an alternative splicing switch that down-regulates a dominant-negative isoform of A-Raf, leading to activation of the Raf-MEK-ERK pathway and cellular transformation.

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Section: Hnrnp A2 Activates the Ras-mapk-erk Pathwaymentioning

confidence: 99%

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Shilo¹,

Hur²,

Denichenko³

et al. 2014

RNA

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“…This protein is implicated in several steps of the precursor messenger RNA processing and in cellular differentiation [47]. Its overexpression was observed in primary carcinomas and metastases [48]; a downregulation of the protein and an increase of its fragmentation could be the result of drug treatments leading to the inhibition of cell proliferation and colony formation. Moreover, the overexpression of heterogeneous nuclear ribonucleoprotein H leads to production in HeLa cells of a proapoptotic alternative splice variant of Bcl-x [Blc-x(S)] [49].…”

Section: Functional Roles Of the Identified Proteinsmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

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We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

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“…Kleine et al reported that H-FABP flowed into the blood after myocardial damage occurred, and thus, H-FABP was available for the detection and assessment of myocardial infarction (24). Rauch et al found that E-FABP was overexpressed in head and neck cancer and was a candidate as a serum marker (25). FABP6 is one of the FABP gene families Bottom, h-actin was used for internal control.…”

Section: Fabp6 Expression In Clinical Samplesmentioning

confidence: 99%

Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer

Ohmachi

Inoue

Mimori

et al. 2006

Clinical Cancer Research

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Purpose: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. Experimental Design: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. Results: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P < 0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P < 0.01), more often in the left colon (P < 0.05), and had shallower invasion into the bowel wall (P < 0.05) compared with those with low expression. There was no significant difference between high-and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P < 0.05), more dominant proliferation (P < 0.001), and less apoptosis than mock cells. Conclusions:The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.

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Allogenic antibody-mediated identification of head and neck cancer antigens

Cited by 64 publications

References 27 publications

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer

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