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Scientific article
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On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm

Published inCell reports, vol. 38, no. 10, 110490
Publication date2022-03-08
First online date2022
Abstract

How metastatic cells arise is unclear. Here, we search for the induction of recently characterized pro-metastatic states as a surrogate for the origin of metastasis. Since cell-death-inducing therapies can paradoxically promote metastasis, we ask if such treatments induce pro-metastatic states in human colon cancer cells. We find that post-near-death cells acquire pro-metastatic states (PAMEs) and form distant metastases in vivo. These PAME ("let's go" in Greek) cells exhibit a multifactorial cytokine storm as well as signs of enhanced endoplasmic reticulum (ER) stress and nuclear reprogramming, requiring CXCL8, INSL4, IL32, PERK-CHOP, and NANOG. PAMEs induce neighboring tumor cells to become PAME-induced migratory cells (PIMs): highly migratory cells that re-enact the storm and enhance PAME migration. Metastases are thus proposed to originate from the induction of pro-metastatic states through intrinsic and extrinsic cues in a pro-metastatic tumoral ecosystem, driven by an impending cell-death experience involving ER stress modulation, metastatic reprogramming, and paracrine recruitment via a cytokine storm.

eng
Keywords
  • ER stress
  • PAME
  • Apoptosis
  • Colon cancer
  • Cytokine storm
  • Metastasis
  • Metastasis-initiating cells
  • Metastatic reprogramming
  • Primary heterogeneity
  • Regulated cell death
Citation (ISO format)
CONOD, Arwen, SILVANO, Marianna, RUIZ ALTABA, Ariel. On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm. In: Cell reports, 2022, vol. 38, n° 10, p. 110490. doi: 10.1016/j.celrep.2022.110490
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ISSN of the journal2211-1247
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Creation04/08/2022 7:52:00 AM
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