title: CD317 Promotes the survival of cancer cells through apoptosis-inducing factor.
abstract: Low nutrient environment is a major obstacle to solid tumor growth. However, many tumors have developed adaptive mechanisms to circumvent the requirement for exogenous growth factors.
  
  
  
  Here we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD317 expression respectively, in mammalian cancer cells, and subjected these CD317-manipulated cells to serum deprivation to study the role of CD317 on stress-induced apoptosis and the underlying mechanism.
  
  
  
  We report that CD317, an innate immune gene overexpressed in human cancers, protected cancer cells against serum deprivation-induced apoptosis. In tumor cells, loss of CD317 markedly enhanced their susceptibility to serum deprivation-induced apoptosis with no effect on autophagy or caspase activation, indicating an autophagy- and caspase-independent mechanism of CD317 function. Importantly, CD317 knockdown in serum-deprived tumor cells impaired mitochondria function and subsequently promoted apoptosis-inducing factor (AIF) release and nuclear translocation but had little effect on mitochondrial and cytoplasmic distributions of cytochrome C, a pro-apoptotic factor released from mitochondria that initiates caspase processing in response to death stimuli. Furthermore, overexpression of CD317 in HEK293T cells inhibits serum deprivation-induced apoptosis as well as the release and nuclear accumulation of AIF.
  
  
  
  Our data suggest that CD317 functions as an anti-apoptotic factor through the mitochondria-AIF axis in malnourished condition and may serve as a potential drug target for cancer therapy.
authors.affiliation: Division of Immunology, School of Fundamental Medicine, Jinzhou Medical University, Jinzhou, 121001, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
authors.forename: Guizhong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
authors.forename: Junxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.|713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Youhai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Immunology, School of Fundamental Medicine, Jinzhou Medical University, Jinzhou, 121001, People's Republic of China. yuguang@lnmu.edu.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China. xc.wan@siat.ac.cn.|Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen University Town, 1068 Xueyuan Avenue, Shenzhen, 518055, People's Republic of China. xc.wan@siat.ac.cn.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D051033:Apoptosis Inducing Factor; D020169:Caspases; D045304:Cytochromes c; D058851:GPI-Linked Proteins; C494829:AIFM1 protein, human; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
keywords: Apoptosis; Apoptosis inducing factor (AIF); CD317