Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

Oncotarget
Hussein F AqbiMasoud H Manjili

Abstract

Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect th...Continue Reading

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Citations

Aug 23, 2019·Cancers·Rana Jahanban-EsfahlanPeyman Zare
Aug 28, 2020·Radiation Research·Nipa H PatelDavid A Gewirtz
Oct 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Botai XuanMichelle R Dawson
Jan 24, 2021·Journal of Cell Science·Timothy MarshJayanta Debnath
Mar 30, 2021·Seminars in Cancer Biology·Kimberly A ParkerWilliam P Schiemann
Apr 1, 2021·Seminars in Cancer Biology·Saeed H ManjiliMasoud H Manjili
Apr 4, 2021·Cells·Wan Najbah Nik NabilHongxi Xu
Apr 6, 2021·Frontiers in Oncology·Yunus AkkocDevrim Gozuacik
Jun 12, 2021·Trends in Cancer·Eileen WhiteJessie Yanxiang Guo
Aug 26, 2021·Journal of Cell Science·Timothy MarshJayanta Debnath
Dec 19, 2021·Journal of Gastrointestinal Cancer·Yunus Akkoc, Devrim Gozuacik

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Methods Mentioned

BETA
flow cytometry
biopsies
Transfection
transgenic
ELISA

Software Mentioned

NDP View

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