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NIH Research Festival

September 14 – 16, 2016

CEBPD facilitates adaptation of human breast cancer cells to endoplasmic reticulum stress

Wednesday, September 14, 2016 – Poster Session I
3:00 – 4:30 p.m.

FAES Terrace

NCI

CANCER-4

Authors

  • N Sheshadri
  • E Sterneck

Abstract

Limiting supply of nutrients and oxygen in tumor cells disrupts protein folding homeostasis resulting in Endoplasmic Reticulum (ER) stress. The accumulation of misfolded proteins triggers a cyto-protective signaling pathway termed the Unfolded Protein Response (UPR) which promotes cell survival by upregulating chaperones, anti-oxidant genes and autophagy. CEBPD is a member of the CCAAT-enhancer binding protein (CEBP) family of transcription factors and is activated in response to acute stressors. While members of the CEBP family associate with UPR transcription factors, the role of CEBPD in this context is yet to be explored. Recent studies associating elevated ER stress with aggressive, hormone-therapy resistant breast cancer prompted us to evaluate the role of CEBPD in this stress response pathway. Using breast cancer cell lines as a model system, we found that acute treatment with chemical and physiological ER stress inducers resulted in a dynamic induction of CEBPD. We found that CEBPD induction was compromised with the use of UPR inhibitors. Further, we show that knockdown of CEBPD in cancer cells caused elevated expression of a transcription factor that mediates ER stress induced cell death, CHOP. CEBPD-silenced cells also exhibited reduced autophagy induction in response to ER stress. Taken together, our data suggests that CEBPD is a novel UPR effector and its expression might provide a survival advantage to cancer cells experiencing ER stress. We plan to evaluate the genes regulated by the CEBPD during ER stress and assess if targeting CEBPD could make cancer cells susceptible to ER stress inducing therapeutics.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021

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Current Research Festival

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    • General Schedule of Events
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