RETRACTED: Role of Autophagy as a Survival Mechanism for Hypoxic Cells in Tumors
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Post-publication record
- Nature
- Retraction
- Reason
- Duplication of/in Image;Falsification/Fabrication of Image;Investigation by Company/Institution;Manipulation of Images;Misconduct - Official Investigation(s) and/or Finding(s);
- Date
- 4/3/2024 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
Enhanced autophagy has been observed in hypoxic regions of solid tumors. Here we address the hypothesis that autophagy is required for survival of hypoxic cells. We evaluated sensitivity to hypoxia of three human tumor cell lines (MCF7, PC3, and LNCaP) and their autophagy-deficient variants with shRNA knockdown of the genes ATG7 and BECLIN1. Hypoxia-induced cell death was more rapid for autophagy-deficient cells and was increased in the presence of the proton pump inhibitor pantoprazole that inhibits autophagy. Autophagy-deficient cells had a lower rate of oxygen consumption than wild-type cells. In xenografts derived from the three cell lines, autophagy (as determined by increased LC3 and reduced p62/SQSTM1) colocalized with hypoxic regions (identified by EF5). Xenografts derived from autophagy-deficient cells grew more slowly than wild-type tumors. Both LC3 expression and hypoxia were decreased in xenografts generated from single-knockdown cells and absent in double-knockdown tumors. Our results are consistent with the hypothesis that autophagy facilitates the survival of hypoxic cells, although reduced oxygen consumption of autophagy-deficient cells may contribute to lack of hypoxia in tumors derived from them. Because hypoxia is associated with resistance to anticancer therapy, inhibition of autophagy has potential to enhance the effectiveness of cancer treatment.
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The record
- Venue
- Neoplasia
- Topic
- Autophagy in Disease and Therapy
- Field
- Medicine
- Canadian institutions
- Princess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
- Funders
- Canadian Institutes of Health Research
- Keywords
- AutophagyGene knockdownHypoxia (environmental)Cancer researchProgrammed cell deathCell cultureBiologySmall hairpin RNACancer cellCell biologyCellChemistryApoptosisCancerOxygenBiochemistryGenetics
- Has abstract in OpenAlex
- yes