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Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy.
Lee, Mi-Gi; Choi, Min-Ah; Chae, Sehyun; Kang, Mi-Ae; Jo, Hantae; Baek, Jin-Myoung; In, Kyu-Ree; Park, Hyein; Heo, Hyojin; Jang, Dongmin; Brito, Sofia; Kim, Sung Tae; Kim, Dae-Ok; Lee, Jong-Soo; Kim, Jae-Ryong; Bin, Bum-Ho.
Afiliación
  • Lee MG; Department of Food Science and Technology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
  • Choi MA; Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu, 42415, Republic of Korea.
  • Chae S; Korea Brain Bank, Korean Brain Research Institute, Daegu, 41062, Republic of Korea.
  • Kang MA; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Jo H; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Baek JM; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • In KR; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Park H; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Heo H; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Jang D; Department of Biomedical Sciences, Major in Molecular Medicine, Ajou University Graduate School, Suwon, South Korea.
  • Brito S; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Kim ST; Department of Pharmaceutical Engineering, Inje University, Gimhae-si, 50834, Korea.
  • Kim DO; Department of Food Science and Technology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
  • Lee JS; Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Republic of Korea.
  • Kim JR; Department of Bological Sciences, Ajou University, Suwon, 443-380, Korea.
  • Bin BH; Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu, 42415, Republic of Korea. kimjr000@gmail.com.
Sci Rep ; 9(1): 15042, 2019 10 21.
Article en En | MEDLINE | ID: mdl-31636298
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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autofagia / Dermis / Proteínas de Transporte de Catión / Fibrosarcoma Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autofagia / Dermis / Proteínas de Transporte de Catión / Fibrosarcoma Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article