title: Upregulation of BNIP3 mediated by ERK/HIF-1α pathway induces autophagy and contributes to anoikis resistance of hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Acquisition of anoikis resistance is the hallmark of cancer and has been shown to be involved in metastasis of melignant cells. Our previous work showed that anoikis resistance is associated with the metastasis of hepatocellular carcinoma (HCC) cells. The aim of this study is to elucidate the mechanisms of this course.
  
  
  METHODS
  Expression of BNIP3 and HIF-1α at the mRNA and protein level in HCC cells were detected by realtime PCR and western blot, respectively. Autophagy activation and signaling transduction pathway were detected by western blot. Cell viabilities were detected by CCK8 assay and trypan blue exclusion assay.
  
  
  RESULTS
  Upregulation of BNIP3 promoted the activation of autophagy, one type of cell survival strategy in response to external stress, by suppressing mTOR/S6K1 signaling system. The upregulation of BNIP3 was mediated by ERK/HIF-1α pathway, which further contributed to anoikis resistance of HCC cells through the mTORC1 signaling pathway.
  
  
  CONCLUSIONS
  Upregulation of BNIP3 contributs to anoikis resistance of HCC cells, and BNIP3 may serve as a novel therapeutic target for manipulation of cancer metastasis.
authors: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors: Lei
authors: L
authors: Sun
authors: Tao
authors: T
authors: Li
authors: Qing
authors: Q
authors: Wei
authors: Ying
authors: Y
authors: Zhang
authors: Xiaoqing
authors: X
authors: Jia
authors: Zhengkun
authors: Z
authors: Wan
authors: Lihui
authors: L
authors: Han
mesh_terms: D023102:Anoikis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C090121:BNIP3 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011518:Proto-Oncogene Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BNIP3; anoikis resistance; autophagy; hepatocellular carcinoma; mTOR/S6K1