Roles of autophagy in breast cancer treatment: Target, bystander or benefactor

Tyutyunyk‐Massey, Liliya; Gewirtz, David A.

doi:10.1016/j.semcancer.2019.11.008

Cited by 31 publications

(25 citation statements)

References 75 publications

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“…There is a complicated interaction between autophagy and breast cancer progression, and the function of autophagy in breast cancer remains unclear [ 3 , 4 ]. Autophagy regulation is considered a possible treatment strategy for TNBC [ 9 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…The generation of cytotoxic autophagy may either lead independently to cell death or act as a precursor to apoptosis [ 3 , 4 ]. In our previous study, we used a pan-caspase inhibitor (z-VAD-fmk) to pretreat MDA-MB-231 cells, which significantly reduced flavopereirine-induced apoptosis from 77.2 to 27.5% at 48 h [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the physiological roles of autophagy, autophagic dysfunction has been identified in the pathogenesis of diverse diseases, including cancer, neurodegeneration, microbial infection, and aging [ 1 ]. In cancer treatment, autophagy also plays a critical role in the survival of breast cancer cells and is considered a novel therapeutic target [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Inducing autophagy was demonstrated to be a potential therapeutic strategy for TNBC treatment [ 9 ]. However, it is still unclear whether autophagy in TNBC has a protective or cytotoxic role [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Chen

Yeh

et al. 2020

IJMS

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Autophagy is a potential target for the treatment of triple negative breast cancer (TNBC). Because of a lack of targeted therapies for TNBC, it is vital to find optimal agents that avoid chemoresistance and metastasis. Flavopereirine has anti-proliferation ability in cancer cells, but whether it regulates autophagy in breast cancer cells remains unclear. A Premo™ Tandem Autophagy Sensor Kit was used to image the stage at which flavopereirine affects autophagy by confocal microscopy. A plasmid that constitutively expresses p-AKT and siRNA targeting p38 mitogen-activated protein kinase (MAPK) was used to confirm the related signaling pathways by Western blot. We found that flavopereirine induced microtubule-associated protein 1 light chain 3 (LC3)-II accumulation in a dose- and time-dependent manner in MDA-MB-231 cells. Confocal florescent images showed that flavopereirine blocked autophagosome fusion with lysosomes. Western blotting showed that flavopereirine directly suppressed p-AKT levels and mammalian target of rapamycin (mTOR) translation. Recovery of AKT phosphorylation decreased the level of p-p38 MAPK and LC3-II, but not mTOR. Moreover, flavopereirine-induced LC3-II accumulation was partially reduced in MDA-MB-231 cells that were transfected with p38 MAPK siRNA. Overall, flavopereirine blocked autophagy via LC3-II accumulation in autophagosomes, which was mediated by the AKT/p38 MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Chen

Yeh

et al. 2020

IJMS

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“…Autophagy has been shown to participate in development, metastasis, progression and drug resistance of breast cancer ( Chen et al, 2019 ; Tracey et al, 2020 ; Tyutyunyk-Massey & Gewirtz, 2019 ; Wang, Yin & Yang, 2019 ). For example, autophagy was activated as a survival mechanism for breast cancer cells following endocrine therapy or HER2-targeted therapy but failed to rescue the cells ( Mele et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy

Zhong

Chen

Yang

et al. 2020

PeerJ

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We aimed to identify prognostic signature based on autophagy-related genes (ARGs) for breast cancer patients. The datasets of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to construct multiple-ARG risk signature. In total, 32 ARGs were identified as differentially expressed between tumors and adjacent normal tissues based on TCGA. Six ARGs (IFNG, TP63, PPP1R15A, PTK6, EIF4EBP1 and NKX2-3) with non-zero coefficient were selected from the 32 ARGs using LASSO regression. The 6-ARG signature divided patients into high-and low-risk group. Survival analysis indicated that low-risk group had longer survival time than high-risk group. We further validated the 6-ARG signature using dataset from GEO and found similar results. We analyzed the associations between ARGs and breast cancer survival in TCGA and nine GEO datasets, and obtained 170 ARGs with significant associations. EIF4EBP1, FOS and FAS were the top three ARGs with highest numbers of significant associations. EIF4EBP1 may be a key ARG which had a higher expression level in patients with more malignant molecular subtypes and higher grade breast cancer. In conclusion, our 6-ARG signature was of significance in predicting of overall survival of patients with breast cancer. EIF4EBP1 may be a key ARG associated with breast cancer survival.

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Construction of a prognostic risk assessment model for HER2 + breast cancer based on autophagy-related genes

Wang

Fang

et al. 2023

Breast Cancer

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Roles of autophagy in breast cancer treatment: Target, bystander or benefactor

Cited by 31 publications

References 75 publications

Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy

Construction of a prognostic risk assessment model for HER2 + breast cancer based on autophagy-related genes

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