Skip to main content

Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses

Publication ,  Conference
Ding, C-KC; Tang, X; Kim, SY; Chi, J-TA
Published in: Cancer Research
August 1, 2015

Increased oxidative stress in the tumor microenvironments is a prominent stress that many tumor cells need to cope with during oncogenesis. The stress depletes intracellular glutathione, increases reactive oxygen species, and finally triggers cell death in tumors. Despite its importance during oncogenesis, the genetic determinants and the cell death mechanisms under oxidative stress remain poorly defined. Here, we applied a genome-wide siRNA screen to oxidative-stress-induced cell death. Candidate genes were identified if the silencing could rescue cell death under oxidative stresses. The identified candidate genes are prioritized by the magnitude of rescue and the consistency among different siRNAs that target the same gene. Selected top hits were further functionally validated using independent siRNAs and chemicals in multiple cancer cell types. To further understand the functional aspects of these genes, we also analyzed the transcriptional and metabolomic response to oxidative stresses. By these functional genomics approach, we found that: 1) The Integrated Stress Response (ISR) is provoked by oxidative stresses to mediate cell death. Therefore, inhibition of IRE1-splicing activity, which is one of the major branches of ISR pathway, could abolish oxidative-stress-induced cell death. 2) Surprisingly, inhibition of multiple component of mTORC1 signaling, including mTOR itself, could rescue oxidative-stress-induced cell death. While further investigation is still in progress, these preliminary findings unravel a unique molecular process in which oxidative stress mediate cell death and the adaptive mechanism by which tumor cells survive these stresses.Citation Format: Chien-Kuang C. Ding, Xiaohu Tang, So Young Kim, Jen-Tsan A. Chi. Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1100. doi:10.1158/1538-7445.AM2015-1100

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 1, 2015

Volume

75

Issue

15_Supplement

Start / End Page

1100 / 1100

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ding, C.-K., Tang, X., Kim, S. Y., & Chi, J.-T. (2015). Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses. In Cancer Research (Vol. 75, pp. 1100–1100). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2015-1100
Ding, Chien-Kuang C., Xiaohu Tang, So Young Kim, and Jen-Tsan A. Chi. “Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses.” In Cancer Research, 75:1100–1100. American Association for Cancer Research (AACR), 2015. https://doi.org/10.1158/1538-7445.am2015-1100.
Ding C-KC, Tang X, Kim SY, Chi J-TA. Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses. In: Cancer Research. American Association for Cancer Research (AACR); 2015. p. 1100–1100.
Ding, Chien-Kuang C., et al. “Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses.” Cancer Research, vol. 75, no. 15_Supplement, American Association for Cancer Research (AACR), 2015, pp. 1100–1100. Crossref, doi:10.1158/1538-7445.am2015-1100.
Ding C-KC, Tang X, Kim SY, Chi J-TA. Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses. Cancer Research. American Association for Cancer Research (AACR); 2015. p. 1100–1100.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 1, 2015

Volume

75

Issue

15_Supplement

Start / End Page

1100 / 1100

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis