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Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy.
- Source :
-
Oncotarget [Oncotarget] 2018 Apr 24; Vol. 9 (31), pp. 22113-22122. Date of Electronic Publication: 2018 Apr 24 (Print Publication: 2018). - Publication Year :
- 2018
-
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 (ATG5 <superscript>KD</superscript> ), 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, ATG5 <superscript>KD</superscript> 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 the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy.<br />Competing Interests: CONFLICTS OF INTEREST Authors have no potential conflicts of interest to disclose.
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 9
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 29774126
- Full Text :
- https://doi.org/10.18632/oncotarget.25197