Dataset Information

The ABCC6 Transporter: A New Player in Biomineralization.

ABSTRACT: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. Since the first description of the disease in 1896, alleging a disease involving the elastic fibers, the concept evolved with the further discoveries of the pivotal role of ectopic mineralization that is preponderant in the elastin-rich tissues of the skin, eyes and blood vessel walls. After discovery of the causative gene of the disease in 2000, the function of the ABCC6 protein remains elusive. More than 300 mutations have been now reported and the concept of a dermal disease has progressively evolved toward a metabolic disorder resulting from the remote effects caused by lack of a circulating anti-mineralization factor. Very recently, evidence has accumulated that this anti-mineralizing factor is inorganic pyrophosphate (PPi). This leads to decreased PPi/Pi (inorganic phosphate) ratio that results from the lack of extracellular ATP release by hepatocytes and probably renal cells harboring the mutant ABCC6 protein. However, the mechanism by which ABCC6 dysfunction causes diminished ATP release remains an enigma. Studies of other ABC transporters, such as ABCC7 or ABCC1 could help our understanding of what ABCC6 exact function is. Data and a hypothesis on the possible roles of ABCC6 in acquired metabolic diseases are also discussed.

SUBMITTER: Favre G

PROVIDER: S-EPMC5618590 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The ABCC6 Transporter: A New Player in Biomineralization.

Favre Guillaume G Laurain Audrey A Aranyi Tamas T Szeri Flora F Fulop Krisztina K Le Saux Olivier O Duranton Christophe C Kauffenstein Gilles G Martin Ludovic L Lefthériotis Georges G

International journal of molecular sciences 20170911 9

Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the <i>ABCC6</i> gene. Since the first description of the disease in 1896, alleging a disease involving the elastic fibers, the concept evolved with the further discoveries of the pivotal role of ectopic mineralization that is preponderant in the elastin-rich tissues of the skin, eyes and blood vessel walls. After discovery of the causative gene of the disease in 2000, the ...[more]

PMID: 28891970

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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: A New Player in Biomineralization.

Publications

The ABCC6 Transporter: A New Player in Biomineralization.

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