FOXO3 links autophagy to apoptosis

Fitzwalter, Brent E.; Thorburn, Andrew

doi:10.1080/15548627.2018.1475819

Cited by 77 publications

(52 citation statements)

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“…Autophagy and apoptosis both play crucial roles in various biological responses [ 35 – 37 ]. Our findings showed that NUCKS knockdown could induce both autophagy and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Zhao

Feng

Bai

et al. 2020

J Exp Clin Cancer Res

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Background Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001, is a member of the high mobility group (HMG) family. Although very little is known regarding the biological roles of NUCKS, emerging clinical evidence suggests that the NUCKS protein can be used as a biomarker and therapeutic target in various human ailments, including several types of cancer. Methods We first assessed the potential correlation between NUCKS expression and gastric cancer prognosis. Then functional experiments were conducted to evaluate the effects of NUCKS in cell proliferation, cell cycle, apoptosis and autophagy. Finally, the roles of NUCKS on gastric cancer were examined in vivo. Results We found that NUCKS was overexpressed in gastric cancer patients with poor prognosis. Through manipulating NUCKS expression, it was observed to be positively associated with cell proliferation in vitro and in vivo. NUCKS knockdown could induce cell cycle arrest and apoptosis. Then further investigation indicated that NUCKS knockdown could also significantly induce a marked increase in autophagy though the mTOR-Beclin1 pathway, which could be was rescued by NUCKS restoration. Moreover, silencing Beclin1 in NUCKS knockdown cells or adding rapamycin in NUCKS-overexpressed cells also confirmed these results. Conclusions Our findings revealed that NUCKS functions as an oncogene and an inhibitor of autophagy in gastric cancer. Thus, the downregulation or inhibition of NUCKS may be a potential therapeutic strategy for gastric cancer.

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“…Autophagy and apoptosis both play crucial roles in various biological responses [ 35 – 37 ]. Our findings showed that NUCKS knockdown could induce both autophagy and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Zhao

Feng

Bai

et al. 2020

J Exp Clin Cancer Res

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“…The mechanisms by which autophagy inhibition leads to cell death have only recently started to be elucidated. When autophagy is inhibited, FOXO3A levels increase expression of the PUMA/BBC3 gene that sensitizes tumor cells to apoptosis induced by an anticancer agent (106). Surprisingly, although other transcription factors also control the PUMA gene and FOXO3 regulates many other genes, mutation of a single FOXO-binding site in the PUMA gene was sufficient to abolish the ability of either HCQ or genetic inhibition of ATG5 or ATG7 to sensitize to anticancer drugs.…”

Section: Determinants Of Autophagy Dependency In Cancermentioning

confidence: 99%

Targeting Autophagy in Cancer: Recent Advances and Future Directions

2019

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Autophagy, a multistep lysosomal degradation pathway that supports nutrient recycling and metabolic adaptation, has been implicated as a process that regulates cancer. Although autophagy induction may limit the development of tumors, evidence in mouse models demonstrates that autophagy inhibition can limit the growth of established tumors and improve response to cancer therapeutics. Certain cancer genotypes may be especially prone to autophagy inhibition. Different strategies for autophagy modulation may be needed depending on the cancer context. Here, we review new advances in the molecular control of autophagy, the role of selective autophagy in cancer, and the role of autophagy within the tumor microenvironment and tumor immunity. We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specifi c autophagy inhibitors for cancer treatment, and review future directions for autophagy research. Signifi cance: Autophagy plays a complex role in cancer, but autophagy inhibition may be an effective therapeutic strategy in advanced cancer. A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefi t from this approach.

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“…The FoxO signaling pathway has been reported to be involved in hypoxia injury in cardiac cells. FOXO3 serves as a surveillance mechanism to detect and correct autophagy flux disruptions as well as ensure that the cells where autophagy is lacking are subjected to apoptosis [ 36 ]. Together, these finding and our results indicate that autophagy and ARGs play an important role in AMI.…”

Section: Discussionmentioning

confidence: 99%

Identification of feature autophagy-related genes in patients with acute myocardial infarction based on bioinformatics analyses

Zhao

Zhang

2020

Bioscience Reports

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Abstract Objective: To identify feature autophagy-related genes (ARGs) in patients with acute myocardial infarction (AMI) and further investigate their value in the diagnosis of AMI. Methods: Gene microarray expression data of AMI peripheral blood samples were downloaded from the GSE66360 dataset. The data were randomly classified into a discovery cohort (21 AMI patients and 22 healthy controls) and a validation cohort (28 AMI patients and 28 healthy controls). Differentially expressed ARGs between patients with AMI and healthy controls in the discovery cohort were identified using a statistical software package. Feature ARGs were screened based on support vector machine-recursive feature elimination (SVM-RFE), and an SVM classifier was constructed. Receiver operating characteristic (ROC) analysis was used to investigate the predictive value of the classifier, which was further verified in an independent external cohort. Results: A total of seven genes were identified based on SVM-RFE. The SVM classifier had an excellent discrimination ability in both the discovery cohort (area under the curve [AUC] = 0.968) and the validation cohort (AUC = 0.992), which was further confirmed in the GSE48060 dataset (AUC = 0.963). Furthermore, the SVM classifier showed outstanding discrimination between AMI patients with and without recurrent events in the independent external cohort (AUC = 0.992). The identified genes are mainly involved in the cellular response to autophagy, macroautophagy, apoptosis, and the FoxO signaling pathway. Conclusion: Our study identified feature ARGs and indicated their potential roles in AMI diagnosis to improve our understanding of the molecular mechanism underlying the occurrence of AMI.

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FOXO3 links autophagy to apoptosis

Cited by 77 publications

References 1 publication

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Targeting Autophagy in Cancer: Recent Advances and Future Directions

Identification of feature autophagy-related genes in patients with acute myocardial infarction based on bioinformatics analyses

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