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

Cell Death & Disease
Eswara Murali SatyavarapuChitra Mandal

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 c...Continue Reading

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Citations

Mar 24, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Xiao-Bao ShenXinhua Liu
Oct 22, 2020·Biochemical Society Transactions·Duhita SenguptaKaushik Sengupta
Sep 3, 2019·The Journal of Investigative Dermatology·Guannan ZhuChunying Li
Mar 16, 2021·Oral Diseases·Anwar A A Y AlMuzainiSunday O Akintoye
Jun 16, 2021·Environmental Science and Pollution Research International·Yuanliang LiYing Li
Aug 18, 2020·European Journal of Pharmacology·Muhammad Furqan AkhtarMohamed M Abdel Daim
Aug 25, 2021·Reproductive Biology·Yinsheng GuoJindou Hao
Aug 21, 2019·Seminars in Cancer Biology·Chandan Kanta DasMahitosh Mandal

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Methods Mentioned

BETA
FACS
co-immunoprecipitation
flow cytometry
transfection
dissection
Antibody Sampler
protein assay
PCR
ELISA
fluorescence microscopy

Software Mentioned

image
graph pad Prism
FACS
CellQuestPro
ImageJ

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