Abstract
Current evidence suggests a significant role of aberrant splicing in the development and maintenance of malignancy. This multistep, tightly regulated epigenetic process leads to the production of abnormal proteins with abnormal functions contributing to underlying mechanisms of malignant transformation. Splicing patterns in malignant cells can be altered not only by the mutations detected on the aberrantly spliced gene, but also by the mutations detected on the genes encoding splicing factors. For example, aberrant pre-mRNA splicing, leading to intracellular or extracellular HA synthesis by HASs, contributes to the initiation and progression of various types of cancer. The influence of intracellular HA appears to be particularly significant and is promoted by aberrant splicing. In this review we report a model describing oncogenic potential of aberrant splicing, with a focus on HAS1 and intracellular HA. We also suggest that the influence of splicing mutations on malignant disease is likely multifactorial. For the triple axis of HA, HAS1 and RHAMM, mutations in HAS1 provide an indicator that these aberrations contribute to the events that lead to malignancy through increased risk and predisposition. Here, we also summarize the impact of splicing abnormalities on cancer and the possible oncogenic impact of aberrantly spliced HAS1. In conclusion, we emphasize that specific gene splice variants and the splicing process itself offer potential targets for novel drug treatment strategies.
Keywords: Alternative splicing, drug targets, hyaluronan, hyaluronan synthases, oncogenesis.
Current Cancer Drug Targets
Title:Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets
Volume: 13 Issue: 4
Author(s): Sophia Adamia, Patrick M. Pilarski, Andrew R. Belch and Linda M. Pilarski
Affiliation:
Keywords: Alternative splicing, drug targets, hyaluronan, hyaluronan synthases, oncogenesis.
Abstract: Current evidence suggests a significant role of aberrant splicing in the development and maintenance of malignancy. This multistep, tightly regulated epigenetic process leads to the production of abnormal proteins with abnormal functions contributing to underlying mechanisms of malignant transformation. Splicing patterns in malignant cells can be altered not only by the mutations detected on the aberrantly spliced gene, but also by the mutations detected on the genes encoding splicing factors. For example, aberrant pre-mRNA splicing, leading to intracellular or extracellular HA synthesis by HASs, contributes to the initiation and progression of various types of cancer. The influence of intracellular HA appears to be particularly significant and is promoted by aberrant splicing. In this review we report a model describing oncogenic potential of aberrant splicing, with a focus on HAS1 and intracellular HA. We also suggest that the influence of splicing mutations on malignant disease is likely multifactorial. For the triple axis of HA, HAS1 and RHAMM, mutations in HAS1 provide an indicator that these aberrations contribute to the events that lead to malignancy through increased risk and predisposition. Here, we also summarize the impact of splicing abnormalities on cancer and the possible oncogenic impact of aberrantly spliced HAS1. In conclusion, we emphasize that specific gene splice variants and the splicing process itself offer potential targets for novel drug treatment strategies.
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Cite this article as:
Adamia Sophia, Pilarski Patrick M., Belch Andrew R. and Pilarski Linda M., Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets, Current Cancer Drug Targets 2013; 13 (4) . https://dx.doi.org/10.2174/1568009611313040001
DOI https://dx.doi.org/10.2174/1568009611313040001 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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