Dataset Information

Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy.

ABSTRACT: Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13^-/- cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13^-/- cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13^-/- cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.

SUBMITTER: Lee MG

PROVIDER: S-EPMC6803768 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy.

Lee Mi-Gi MG Choi Min-Ah MA Chae Sehyun S Kang Mi-Ae MA Jo Hantae H Baek Jin-Myoung JM In Kyu-Ree KR Park Hyein H Heo Hyojin H Jang Dongmin D Brito Sofia S Kim Sung Tae ST Kim Dae-Ok DO Lee Jong-Soo JS Kim Jae-Ryong JR Bin Bum-Ho BH

Scientific reports 20191021 1

Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably express ...[more]

PMID: 31636298

Similar Datasets

Project description:eLife digestIron is essential for life. Amongst its many important roles, iron is crucial for producing collagen—the protein that provides both strength and elasticity to bones, tendons, ligaments, and skin. Like many other proteins, collagens are produced inside the endoplasmic reticulum—an organelle inside the cell that is enclosed by a membrane that is similar to the plasma membrane that surrounds the cell itself.Two enzymes that are critical for producing collagen need to bind with iron in order to work correctly. To do this, iron in the cytoplasm of the cell has to cross the membrane that surrounds the endoplasmic reticulum. Small molecules are commonly transported across membranes by proteins called transporters, which tend to work on specific types of ions or molecules. However, researchers did not know the identity of the membrane transporter responsible for moving iron into the secretory pathway—including the endoplasmic reticulum—to bind with the enzymes that produce collagen.Xiao, Wan et al. have now investigated the function of the transporter ZIP13 in the fruit fly Drosophila. This transporter was thought to transport zinc across membranes and into the cytoplasm. Instead, Xiao, Wan et al. found that ZIP13 transports iron out of the cytoplasm and into the endoplasmic reticulum.Ehlers–Danlos syndrome is a condition that causes individuals to suffer from frequent joint dislocations, bone deformities, and fragile skin as a result of their body producing collagen incorrectly. One form of Ehlers–Danlos syndrome is caused by ZIP13 transporters working incorrectly. However, this was difficult to understand when it was thought that ZIP13 only transports zinc. The discovery that ZIP13 mostly transports iron rather than zinc can explain the link between this transporter and Ehlers–Danlos syndrome: if ZIP13 doesn't work, the collagen-building enzymes cannot get the iron they need to work properly.Disorders caused by iron deficiencies are normally identified by a few tell-tale symptoms, such as anemia, but these are not seen in Ehlers–Danlos syndrome. Xiao, Wan et al. suggest that iron transport problems could therefore be behind a wider range of diseases and disorders than is currently known.DOI: http://dx.doi.org/10.7554/eLife.03191.002

Dataset Information

Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy.

Publications

Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets