Evidence map›Paper›PMID 30224639›Full record

ArticleCell death & disease2018

Autophagy-independent induction of LC3B through oxidative stress reveals its non-canonical role in anoikis of ovarian cancer cells.

Eswara Murali Satyavarapu, Ranjita Das, Chandan Mandal, Asima Mukhopadhyay, Chitra Mandal

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 74 citations in OpenAlex.

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  18. Mitochondrial ProteinFrontiers in pharmacology · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 5 institutions in 2 countries.

Eswara Murali SatyavarapuCancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4, Raja S.C. Mallick Road, Kolkata, 700032, India.
Ranjita DasBose Institute, P 1/12, C. I. T. Road, Scheme - VIIM, Kolkata, 700054, India.
Chandan MandalTata Medical Center, 14 MAR, Rajarhat, Kolkata, 700156, India.
Asima MukhopadhyayTata Medical Center, 14 MAR, Rajarhat, Kolkata, 700156, India.
Chitra MandalCancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4, Raja S.C. Mallick Road, Kolkata, 700032, India. chitra_mandal@yahoo.com.
Bose Institute · INCouncil of Scientific and Industrial Research · INIndian Institute of Chemical Biology · INNewcastle University · GBTata Medical Center · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer cells display abnormal redox metabolism. Autophagy, anoikis and reactive oxygen species (ROS) play a regulatory role during metastasis. LC3 is a well-known essential molecule for autophagy. Therefore, we wanted to explore the molecular interplay between autophagy, anoikis, and ROS in relation to LC3B. We observed enhanced LC3B level along with increased expression of p62 and modulation of other autophagy-related molecules (Atg 3, 5, 7, 12, 16L1 and Beclin1) by inducing oxidative-stress in ovarian cancer cells using a ROS-producing pro-oxidant molecule. Surprisingly, enhanced LC3B was unable to induce autophagosome formation rather promoted anoikis. ROS-induced inhibition of autophagosome-formation is possibly due to the instability of autophagy initiator, ULK1 complex. Moreover, such upregulation of LC3B via ROS enhanced several apoptotic molecules. Silencing LC3B reduced these apoptotic molecules and increased when overexpressed, suggesting its role in apoptosis. Furthermore, LC3B-dependent apoptosis was decreased by inhibiting ROS, indicating a possible link between ROS, LC3B, and apoptosis. Additionally, ROS-induced enhanced LC3B promoted detachment-induced cell death (anoikis). This was further reflected by reduced cell adhesion molecules (integrin-β3 and focal adhesion kinase) and mesenchymal markers (snail and slug). Our in vitro experimental data was further confirmed in primary tumors developed in syngeneic mice, which also showed ROS-mediated LC3B enhancement along with reduced autophagosomes, integrin-β3 and focal adhesion kinase ultimately leading to the decreased tumor mass. Additionally, primary cells from high-grade serous carcinoma patient's ascites exhibited LC3B enhancement and autophagy inhibition through ROS which provided a clinical relevance of our study. Taken together, this is the first evidence for a non-canonical role of LC3B in promoting anoikis in contrast to autophagy and may, therefore, consider as a potential therapeutic target molecule in ovarian cancer. Taken together, autophagy-inhibition may be an alternative approach to induce apoptosis/anoikis in cancer.

Indexed as

AnimalsAnoikisAutophagyCell Line, TumorCell ProliferationCell SurvivalFemaleHumansMiceMicrotubule-Associated ProteinsOvarian NeoplasmsOxidative StressReactive Oxygen SpeciesMAP1LC3B protein, humanMap1lc3b protein, mouseMicrotubule-Associated ProteinsReactive Oxygen Species

Identifiers

PMID30224639
PMCPMC6141567
OpenAlexW2890738628

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.