Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells

Jacqueline Thorburn, Leah Staskiewicz, Megan L. Goodall, Lina Dimberg, Arthur E. Frankel, Heide L. Ford, Andrew Thorburn

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Autophagy, the mechanism by which cells deliver material to the lysosome, has been associated with resistance to anticancer drugs, leading autophagy inhibition to be widely studied as a potential chemosensitization strategy for cancer cells. This strategy is based on the idea that inhibition of autophagy will increase drug sensitivity and kill more cancer cells. Here we report an unintended negative effect of this strategy. When modeling the effect of drug resistance in a heterogeneous cancer cell population, we found that autophagy inhibition in drug-sensitive tumor cells causes increased growth of drug-resistant cells in the population through a mechanism involving caspase activation and prostaglandin E2 signaling. These results emphasize the importance of understanding how autophagy manipulation in a tumor cell can have both cell-autonomous and nonautonomous effects and suggest that attempts to chemosensitize by inhibiting autophagy could be enhanced by adopting methods aimed at reducing tumor repopulation.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalMolecular Pharmacology
Volume91
Issue number1
StatePublished - Jan 1 2017

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Autophagy
Growth
Pharmaceutical Preparations
Neoplasms
Caspases
Lysosomes
Dinoprostone
Drug Resistance
Population

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Pharmacology

Cite this

Thorburn, J., Staskiewicz, L., Goodall, M. L., Dimberg, L., Frankel, A. E., Ford, H. L., & Thorburn, A. (2017). Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells. Molecular Pharmacology, 91(1), 58-64.

Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells. / Thorburn, Jacqueline; Staskiewicz, Leah; Goodall, Megan L.; Dimberg, Lina; Frankel, Arthur E.; Ford, Heide L.; Thorburn, Andrew.

In: Molecular Pharmacology, Vol. 91, No. 1, 01.01.2017, p. 58-64.

Research output: Contribution to journalArticle

Thorburn, J, Staskiewicz, L, Goodall, ML, Dimberg, L, Frankel, AE, Ford, HL & Thorburn, A 2017, 'Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells', Molecular Pharmacology, vol. 91, no. 1, pp. 58-64.
Thorburn, Jacqueline ; Staskiewicz, Leah ; Goodall, Megan L. ; Dimberg, Lina ; Frankel, Arthur E. ; Ford, Heide L. ; Thorburn, Andrew. / Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells. In: Molecular Pharmacology. 2017 ; Vol. 91, No. 1. pp. 58-64.
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