Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect DOI Creative Commons
Su Min Lim, Ezanee Azlina Mohamad Hanif, Siok‐Fong Chin

et al.

Cell & Bioscience, Journal Year: 2021, Volume and Issue: 11(1)

Published: March 20, 2021

Abstract Autophagy is a conserved cellular process required to maintain homeostasis. The hallmark of autophagy the formation phagophore that engulfs cytosolic materials for degradation and recycling synthesize essential components. Basal constitutively active under normal conditions it could be further induced by physiological stimuli such as hypoxia, nutrient starvation, endoplasmic reticulum stress,energy depletion, hormonal stimulation pharmacological treatment. In cancer, highly context-specific depending on cell type, tumour microenvironment, disease stage external stimuli. Recently, emerging role double-edged sword in cancer has gained much attention. On one hand, suppresses malignant transformation limiting production reactive oxygen species DNA damage during development. Subsequently, evolved support survival cells promotes tumourigenicity stem at established sites. Hence, an attractive target therapeutics researchers have been exploiting use modulators adjuvant therapy. this review, we present summary mechanism controlling pathways, with emphasis dual-role (double-edged sword) cancer. This followed overview modulation treatment concluded discussion current perspectives future outlook exploitation precision medicine.

Language: Английский

A brief history of autophagy from cell biology to physiology and disease DOI
Noboru Mizushima

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(5), P. 521 - 527

Published: April 19, 2018

Language: Английский

Citations

608

The functional universe of membrane contact sites DOI
William A. Prinz,

Alexandre Toulmay,

Tamás Balla

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(1), P. 7 - 24

Published: Nov. 15, 2019

Language: Английский

Citations

567

Regulated cell death (RCD) in cancer: key pathways and targeted therapies DOI Creative Commons
Peng Fu,

Minru Liao,

Rui Qin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 13, 2022

Regulated cell death (RCD), also well-known as programmed (PCD), refers to the form of that can be regulated by a variety biomacromolecules, which is distinctive from accidental (ACD). Accumulating evidence has revealed RCD subroutines are key features tumorigenesis, may ultimately lead establishment different potential therapeutic strategies. Hitherto, targeting with pharmacological small-molecule compounds been emerging promising avenue, rapidly progressed in many types human cancers. Thus, this review, we focus on summarizing not only apoptotic and autophagy-dependent signaling pathways, but crucial pathways other subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis lysosome-dependent (LCD) cancer. Moreover, further discuss current situation several improve cancer treatment, such single-target, dual or multiple-target compounds, drug combinations, some new strategies would together shed light future directions attack vulnerabilities drugs for purposes.

Language: Английский

Citations

506

Autophagy in kidney homeostasis and disease DOI
Chengyuan Tang, Man J. Livingston, Zhiwen Liu

et al.

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 16(9), P. 489 - 508

Published: July 23, 2020

Language: Английский

Citations

372

Diverse Cellular Roles of Autophagy DOI Open Access
Hideaki Morishita, Noboru Mizushima

Annual Review of Cell and Developmental Biology, Journal Year: 2019, Volume and Issue: 35(1), P. 453 - 475

Published: July 8, 2019

Macroautophagy is an intracellular degradation system that delivers diverse cytoplasmic materials to lysosomes via autophagosomes. Recent advances have enabled identification of several selective autophagy substrates and receptors, greatly expanding our understanding the cellular functions autophagy. In this review, we describe macroautophagy, including its essential contribution metabolic adaptation homeostasis. We also discuss emerging findings on mechanisms various types

Language: Английский

Citations

328

Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life DOI Creative Commons

Yoomi Chun,

Joungmok Kim

Cells, Journal Year: 2018, Volume and Issue: 7(12), P. 278 - 278

Published: Dec. 19, 2018

Autophagy is a lysosome-dependent cellular degradation program that responds to variety of environmental and stresses. It an evolutionarily well-conserved essential pathway maintain homeostasis, therefore, dysfunction autophagy closely associated with wide spectrum human pathophysiological conditions including cancers neurodegenerative diseases. The discovery characterization the kingdom proteins have uncovered molecular basis process. In addition, recent advances on various post-translational modifications shed light multiple layers regulatory mechanisms, provide novel therapeutic targets for treatment

Language: Английский

Citations

327

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy DOI Creative Commons
Hongtao Chen, Hao Liu, Minjie Mao

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: May 24, 2019

Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote suppress tumor development, so it "double-edged sword" in tumors depends on the cell tissue types stages tumor. The epithelial-mesenchymal transition (EMT) complex biological trans-differentiation allows epithelial cells to transiently obtain mesenchymal features, including motility metastatic potential. EMT considered an important contributor invasion metastasis cancers. Thus, clarifying crosstalk between autophagy will provide novel targets for cancer therapy. was reported EMT-related signal pathways have impact autophagy; conversely, activation strengthen by regulating various signaling pathways. On one hand, provides energy basic nutrients during spreading, which assists survive stressful environmental intracellular conditions. other autophagy, acting cancer-suppressive function, inclined hinder selectively down-regulating critical transcription factors early phases. Therefore, inhibition inhibitors activators might be strategy thought enlightenment treatment cancer. In this article, we discuss detail role development cancers, regulatory mechanisms EMT, effects potential applications anticancer

Language: Английский

Citations

265

How autophagy controls the intestinal epithelial barrier DOI Open Access
Elisabeth G. Foerster, Tapas Mukherjee,

Liliane Cabral-Fernandes

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 18(1), P. 86 - 103

Published: April 27, 2021

Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well the destruction intracellular pathogens. Its role maintenance intestinal epithelium particular interest, several autophagy-related genes have been associated with disease. Autophagy its regulatory mechanisms are involved both homeostasis repair intestine, supporting barrier function response to stress through tight junction regulation protection from cell death. Furthermore, clear has emerged for autophagy not only secretory cells but also stem cells, where it affects their metabolism, proliferative regenerative capacity. Here, we review physiological context epithelial how genetic mutations affecting contribute development

Language: Английский

Citations

247

Cell death pathways: intricate connections and disease implications DOI

Matthias Kist,

Domagoj Vucic

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(5)

Published: Jan. 13, 2021

Language: Английский

Citations

246

The Emerging Roles of mTORC1 in Macromanaging Autophagy DOI Open Access
Akpedje Serena Dossou, Alakananda Basu

Cancers, Journal Year: 2019, Volume and Issue: 11(10), P. 1422 - 1422

Published: Sept. 24, 2019

Autophagy is a process of self-degradation that enables the cell to survive when faced with starvation or stressful conditions. The mechanistic target rapamycin (mTOR), also known as mammalian rapamycin, plays critical role in maintaining balance between cellular anabolism and catabolism. mTOR complex 1 (mTORC1) was unveiled master regulator autophagy since inhibition mTORC1 required initiate process. Evidence has emerged recent years indicate directly regulates subsequent steps process, including nucleation, autophagosome elongation, maturation termination. By phosphorylating select protein targets core machinery and/or their regulators, can alter functions, increase proteasomal degradation modulate acetylation status, which key switch Moreover, it phosphorylates alters subcellular localization transcription factors suppress expression genes needed for formation lysosome biogenesis. purpose this review article critically analyze current literatures provide an integrated view how various

Language: Английский

Citations

239