Dataset Information

The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

ABSTRACT: The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

SUBMITTER: De Vilder EY

PROVIDER: S-EPMC4555454 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

De Vilder Eva Y G EY Hosen Mohammad Jakir MJ Vanakker Olivier M OM

BioMed research international 20150818

The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as ...[more]

PMID: 26356190

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Project description:The ATP binding cassette (ABC) transporter family is widely distributed in vertebrates and is essential for drug resistance, cell signaling and energy homeostasis. There is growing evidence that various ABC transporters contribute to the growth and development of tumors but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC). ABCC6 transporter was downregulated in HCC tissues and that it was associated with successful treatment for HCC patients. Cellular model studies have shown that ABCC6 plays a role in the migration and cytoskeleton rearrangement of HepG2 hepatocarcinoma cells, highlighting its role in cancer biology. Abcc6-silenced HepG2 cells are used as cell model to obtain more deep information about the molecular mechanisms underlying the observed results. MTT and colony formation assays, showed the effects of Abcc6 on HepG2 cell proliferation. Western blotting analysis, real-time PCR, and immunofluorescence were used to find the E-cadherin, Vimentin, and N-cadherin markers associated with the epithelial-to-mesenchymal transition (EMT). Colony formation experiments in the current study showed that Abcc6 decreased HepG2 cell viability. The migratory and invasion activities were dramatically slowed down by Abcc6 silencing, according to the Transwell and wound-healing assays. In tumor cells, EMT has been shown to be crucial for enhancing migration and invasion and is frequently characterized by a loss of epithelial markers (E-cadherin) and an increase in mesenchymal markers (Vimentin and N-cadherin). In the western blotting examination, E-cadherin expression was considerably elevated compared to the control group, while N-cadherin and Vimentin expression were downregulated. This led to the hypothesis that the underlying mechanism of Abcc6 knockdown prevents migration and invasion in HepG2 cells and is linked to the suppression of EMT. In conclusion all evidence suggested that ABC transporters play a more active role in cancer biology.

Dataset Information

The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

Publications

The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

Similar Datasets

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