Regulation of tumor–stroma interactions by the unfolded protein response

Joanna Obacz, Tony Avril, Camila Rubio-Patiño, Jozef P. Bossowski, Aeid Igbaria, Jean Ehrland Ricci, Eric Chevet

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations

Abstract

The unfolded protein response (UPR) is a conserved adaptive pathway that helps cells cope with the protein misfolding burden within the endoplasmic reticulum (ER). Imbalance between protein folding demand and capacity in the ER leads to a situation called ER stress that is often observed in highly proliferative and secretory tumor cells. As such, activation of the UPR signaling has emerged as a key adaptive mechanism promoting cancer progression. It is becoming widely acknowledged that, in addition to its intrinsic effect on tumor biology, the UPR can also regulate tumor microenvironment. In this review, we discuss how the UPR coordinates the crosstalk between tumor and stromal cells, such as endothelial cells, normal parenchymal cells, and immune cells. In addition, we further describe the involvement of ER stress signaling in the response to current treatments as well as its impact on antitumor immunity mainly driven by immunogenic cell death. Finally, in this context, we discuss the relevance of targeting ER stress/UPR signaling as a potential anticancer approach.

Original languageEnglish
Pages (from-to)279-296
Number of pages18
JournalFEBS Journal
Volume286
Issue number2
DOIs
StatePublished - Jan 2019
Externally publishedYes

Keywords

  • ER stress
  • immunogenic cell death
  • inflammation
  • tumor microenvironment
  • unfolded protein response

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