Adaptive F-Actin Polymerization and Localized ATP Production Drive Basement Membrane Invasion in the Absence of MMPs - Sorbonne Université
Journal Articles Developmental Cell Year : 2019

Adaptive F-Actin Polymerization and Localized ATP Production Drive Basement Membrane Invasion in the Absence of MMPs

Eric Hastie
  • Function : Author
Adam Schindler
  • Function : Author
Yue Jiang
  • Function : Author
  • PersonId : 992294
David Matus
  • Function : Author
Julie Plastino
David Sherwood
  • Function : Author

Abstract

Matrix metalloproteinases (MMPs) are associated with decreased patient prognosis, but have failed as anti-invasive drug targets despite promoting cancer cell invasion. Through time-lapse imaging, optical highlighting, and combined genetic removal of the five MMPs expressed during anchor cell (AC) invasion in C. elegans, we find that MMPs hasten invasion by degrading basement membrane (BM). Though irregular and delayed, AC invasion persists in MMP-animals via adaptive enrichment of the Arp2/3 complex at the invasive cell membrane, which drives formation of an F-actin-rich protrusion that physically breaches and displaces BM. Using a largescale RNAi synergistic screen and a genetically encoded ATP FRET sensor, we discover that mitochondria enrich within the protrusion and provide localized ATP that fuels F-actin network growth. Thus, without MMPs an invasive cell can alter its BM breaching tactics, suggesting that targeting adaptive mechanisms will be necessary to mitigate BM invasion in human pathologies.
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Dates and versions

hal-02410061 , version 1 (02-12-2020)

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Laura C Kelley, Qiuyi Chi, Rodrigo Cáceres, Eric Hastie, Adam Schindler, et al.. Adaptive F-Actin Polymerization and Localized ATP Production Drive Basement Membrane Invasion in the Absence of MMPs. Developmental Cell, 2019, 48 (3), pp.313-328.e8. ⟨10.1016/j.devcel.2018.12.018⟩. ⟨hal-02410061⟩
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