Influence of autophagy on the efficacy of radiotherapy

Tam, Shing Yau; Wu, Vincent; Law, Helen Ka Wai

doi:10.1186/s13014-017-0795-y

Cited by 89 publications

(58 citation statements)

References 36 publications

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“…In many tumors, there is altered expression and/or subcellular localization of autophagy-regulatory proteins [22][23][24][25][26]. As apoptosis contributes to only 20% or less of radiation-induced cell death, there is a great deal of interest in understanding the role of autophagy in regulating IR-induced cell death [27,28]. However, those studies have yielded conflicting results.…”

Section: Introductionmentioning

confidence: 99%

USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination

et al. 2018

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ATG7: autophagy related 7; CQ: chloroquine; DDR: DNA damage response; DUB: deubiquitinase; HR: homologous recombination; IR: ionizing radiation; IRIF: ionizing radiation-induced foci; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MIU1: motif interacting with ubiquitin; NHEJ: non homologous end-joining; PCa: prostate cancer; TP53BP1/53BP1: tumor protein p53 binding protein 1; RNF168: ring finger protein 168; SQSTM1/p62 sequestosome 1; γH2AFX/γH2AX: H2A histone family member X: phosphorylated, UBA: ubiquitin-associated; Ub: ubiquitin; Ubn: ubiquitination; USP14: ubiquitin specific peptidase 14.

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Section: Introductionmentioning

confidence: 99%

USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination

et al. 2018

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“…Autophagy plays a cytoprotective or pro-survival role in cancer cells and can be induced by most cancer treatments including radiation therapy [254][255][256], chemotherapy [257,258], histone deacetylase inhibitors in colon cancer cells [259], arsenic trioxide (As2O3) in malignant glioma cells [260,261], Temozolomide (TMZ) in malignant glioma cells [262], γ-irradiation in breast cancer, prostate cancer, colon cancer and malignant glioma [263][264][265], resveratrol in ovarian cancer [266], TNFα in breast cancer cells [267], IFNγ in Hepatocellular carcinoma (HCC) [268], imatinib lung carcinoma cell [269], rapamycin in malignant glioma cells [270], and tamoxifen in breast cancer and Glioblastoma [271,272], and the autophagy, in turn, functions as a cellular defense and protection mechanism to prevent cancer cell death upon treatment, enable a state of dormancy in residual cancer cells post treatment, contribute to cancer recurrence and metastasis, and inhibit cancer therapy and tumor cell killing [246,273].…”

Section: Autophagy Inhibit Cancer Therapymentioning

confidence: 99%

Autophagy and autophagy-related proteins in cancer

2020

Mol Cancer

1,102

792

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Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy.

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“…It is usually a cytoprotective process, but autophagic cell death occurs when the autophagic response is excessive (Kroemer and Levine, 2008). The autophagic machinery is a highly regulated pathway involving the ATG genes and is known to be triggered by irradiation, likely via the endoplasmic stress module and mTOR pathway, although the exact mechanisms are unclear (Tam et al, 2017). Autophagy observed after irradiation may be a mechanism of treatment resistance or of cell death, being likely context-dependent (Levy et al, 2017;Dikic and Elazar, 2018).…”

Section: Autophagymentioning

confidence: 99%

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Sia

Szmyd

Hau

et al. 2020

Front. Cell Dev. Biol.

270

184

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Radiation therapy (RT) is responsible for at least 40% of cancer cures, however treatment resistance remains a clinical problem. There have been recent advances in understanding the molecular mechanisms of radiation-induced cell death. The type of cell death after radiation depends on a number of factors including cell type, radiation dose and quality, oxygen tension, TP53 status, DNA repair capacity, cell cycle phase at time of radiation exposure, and the microenvironment. Mitotic catastrophe (a pathway preceding cell death that happens in mitosis or as a consequence of aberrant mitotic progression) is the primary context of radiation-induced cell death in solid cancers, although in a small subset of cancers such as haematopoietic malignancies, radiation results in immediate interphase apoptosis, occurring within hours after exposure. There is intense therapeutic interest in using stereotactic ablative body radiotherapy (SABR), a precise, high-dose form of RT given in a small number of fractions, to prime the immune system for cancer cell killing, but the optimal radiation dose and fractionation remain unclear. Additionally, promising novel radiosensitisers targeting the cell cycle and DNA repair pathways are being trialled. In the context of the increasing use of SABR and such novel agents in the clinic, we provide an updated primer on the major types of radiation-induced cell death, focussing on their molecular mechanisms, factors affecting their initiation, and their implications on immunogenicity.

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Influence of autophagy on the efficacy of radiotherapy

Cited by 89 publications

References 36 publications

USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination

USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination

Autophagy and autophagy-related proteins in cancer

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

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