Anticipatory UPR Activation: A Protective Pathway and Target in Cancer

David J. Shapiro, Mara Livezey, Liqun Yu, Xiaobin Zheng, Neal Andruska

Research output: Contribution to journalReview article

Abstract

The endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), plays a key role in regulating intracellular protein homeostasis. The extensively studied reactive mode of UPR activation is characterized by unfolded protein, or other EnR stress, triggering UPR activation. Here we focus on the emerging anticipatory mode of UPR activation in which mitogenic steroid and peptide hormones and other effectors preactivate the UPR and anticipate a future need for increased protein folding capacity. Mild UPR activation in breast cancer can be protective and contributes to antiestrogen resistance. Hyperactivation of the anticipatory UPR pathway in cancer cells with a small molecule converts it from cytoprotective to cytotoxic, highlighting its potential as a therapeutic target in estrogen receptor-positive breast cancer.

Original languageEnglish (US)
Pages (from-to)731-741
Number of pages11
JournalTrends in Endocrinology and Metabolism
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Unfolded Protein Response
Neoplasms
Endoplasmic Reticulum Stress
Breast Neoplasms
Protein Unfolding
Estrogen Receptor Modulators
Peptide Hormones
Protein Folding
Estrogen Receptors
Homeostasis
Steroids

Keywords

  • BHPI
  • cancer
  • estrogen
  • unfolded protein response

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Anticipatory UPR Activation : A Protective Pathway and Target in Cancer. / Shapiro, David J.; Livezey, Mara; Yu, Liqun; Zheng, Xiaobin; Andruska, Neal.

In: Trends in Endocrinology and Metabolism, Vol. 27, No. 10, 01.10.2016, p. 731-741.

Research output: Contribution to journalReview article

Shapiro, David J. ; Livezey, Mara ; Yu, Liqun ; Zheng, Xiaobin ; Andruska, Neal. / Anticipatory UPR Activation : A Protective Pathway and Target in Cancer. In: Trends in Endocrinology and Metabolism. 2016 ; Vol. 27, No. 10. pp. 731-741.
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