title: Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer cells.
abstract: Hypoxia, a critical regulator of tumor growth and metastasis, induces the transcriptional activation of several pathways involved in proliferation, migration and invasion. Gankyrin was found to be overexpressed, and also promoted the metastasis in breast cancer cells, which is also involved in the regulation of hypoxia inducible factor‑1 and hypoxia‑inducible factor‑1α. The present study showed that gankyrin mRNA and protein expression were increased under hypoxic conditions in the BT474 breast cancer cell line, accompanied with increased ability of cell migration and invasion. Lentivirus‑mediated siRNA targeting gankyrin was transfected into BT474 cells. Wound‑healing and transwell experiments showed that gankyrin deletion abrogated the increased migration and invasion of BT474 cells due to hypoxia. In addition, E‑cadherin was found to be involved in the gankyrin induced invasion of breast cancer cells due to hypoxia. The present study indicated that gankyrin deletion abrogated the increased metastatic potential of breast cancer cells under hypoxic conditions partly through regulating E‑cadherin, suggesting that an improved understanding of gankyrin may offer a potential therapeutic target for the treatment of human breast cancer metastasis.
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Liucun
authors: L
authors: Gao
authors: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Huahong
authors: H
authors: Xie
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Lihou
authors: L
authors: Dong
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Jia
authors: J
authors: Zou
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Jie
authors: J
authors: Fu
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Xin
authors: X
authors: Gao
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Lun
authors: L
authors: Ou
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Shensi
authors: S
authors: Xiang
authors: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
authors: Haifeng
authors: H
authors: Song
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015820:Cadherins / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D015820:Cadherins; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D046988:Proteasome Endopeptidase Complex