Cargando…

CD317 Promotes the survival of cancer cells through apoptosis-inducing factor

BACKGROUND: 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. METHODS: Here we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD31...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Xin, Zhang, Guizhong, Chen, Qian, Lin, Yingxue, Li, Junxin, Ruan, Qingguo, Chen, Youhai, Yu, Guang, Wan, Xiaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957287/
https://www.ncbi.nlm.nih.gov/pubmed/27444183
http://dx.doi.org/10.1186/s13046-016-0391-2
_version_ 1782444152921784320
author Li, Xin
Zhang, Guizhong
Chen, Qian
Lin, Yingxue
Li, Junxin
Ruan, Qingguo
Chen, Youhai
Yu, Guang
Wan, Xiaochun
author_facet Li, Xin
Zhang, Guizhong
Chen, Qian
Lin, Yingxue
Li, Junxin
Ruan, Qingguo
Chen, Youhai
Yu, Guang
Wan, Xiaochun
author_sort Li, Xin
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0391-2) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4957287
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-49572872016-07-23 CD317 Promotes the survival of cancer cells through apoptosis-inducing factor Li, Xin Zhang, Guizhong Chen, Qian Lin, Yingxue Li, Junxin Ruan, Qingguo Chen, Youhai Yu, Guang Wan, Xiaochun J Exp Clin Cancer Res Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0391-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-22 /pmc/articles/PMC4957287/ /pubmed/27444183 http://dx.doi.org/10.1186/s13046-016-0391-2 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Li, Xin
Zhang, Guizhong
Chen, Qian
Lin, Yingxue
Li, Junxin
Ruan, Qingguo
Chen, Youhai
Yu, Guang
Wan, Xiaochun
CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title_full CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title_fullStr CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title_full_unstemmed CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title_short CD317 Promotes the survival of cancer cells through apoptosis-inducing factor
title_sort cd317 promotes the survival of cancer cells through apoptosis-inducing factor
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957287/
https://www.ncbi.nlm.nih.gov/pubmed/27444183
http://dx.doi.org/10.1186/s13046-016-0391-2
work_keys_str_mv AT lixin cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT zhangguizhong cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT chenqian cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT linyingxue cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT lijunxin cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT ruanqingguo cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT chenyouhai cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT yuguang cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor
AT wanxiaochun cd317promotesthesurvivalofcancercellsthroughapoptosisinducingfactor