title: Anticipatory UPR Activation: A Protective Pathway and Target in Cancer.
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.
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA. Electronic address: djshapir@life.illinois.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Shapiro
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Livezey
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA; College of Medicine, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Andruska
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology*
keywords: BHPI; cancer; estrogen; unfolded protein response