A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis

Qu, Junsheng; Luo, Moyi; Zhang, Jingwen; Han, Fang; Hou, Ningning; Pan, Ruiyan; Sun, Xiaodong

doi:10.1186/s12935-021-02317-9

Cited by 16 publications

(11 citation statements)

References 92 publications

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“…In exercised mice, Crisol et al [24] have reported that sestrin-1 expression in muscle was increased when acute exercise was performed, whereas chronic exercise provoked its diminution. Likewise, contradictory results have been described for sestrin-2 and tumor pathology, since bidirectional functions (as tumor-suppressing and oncogene) have been found for this protein in various cancer types [46].…”

Section: Discussionmentioning

confidence: 99%

Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes

Sanz

Rezola-Pardo

Arrieta

et al. 2022

IJERPH

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Given the increasing prevalence of frailty and its implications for public health, the identification of biomarkers to detect frailty is essential. Sestrin-1 is a protein with a protective role in muscle function. This study aimed to determine whether the serum sestrin-1 concentration differed between frail and non-frail populations and to investigate its association with frailty-related variables in 225 older women and men living in nursing homes (Gipuzkoa, Spain). Serum sestrin-1 concentration was measured by ELISA. Frailty, dependence, anthropometry, physical function, and physical activity were determined by validated tests and tools. The associations between sestrin-1 concentration and the other variables were determined using generalized linear models. The differences between frail and non-frail individuals were analyzed by the Mann–Whitney U-test, and receiver operating characteristic (ROC) curves were constructed to calculate the capability of sestrin-1 to detect frailty. Unexpectedly, frail individuals—according to the Fried Frailty Phenotype or the Clinical Frailty Scale—had higher serum sestrin-1 concentrations than non-frail individuals. Furthermore, the higher serum sestrin-1 concentration was associated with the increased frailty scores and dependence as well as the poorer physical function and the less physical activity. Given the contradictory results regarding serum sestrin-1 and frailty, further investigation is required to propose it as a molecular biomarker of frailty.

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Section: Discussionmentioning

confidence: 99%

Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes

Sanz

Rezola-Pardo

Arrieta

et al. 2022

IJERPH

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“…2) Sestrin 2 is a probable biomarker and therapeutic target for tumor treatment that plays a vital role in the incidence and development of malignance. Some studies identified sestrin 2 as a tumor suppressor gene, while others described it as an oncogene ( Qu et al, 2021 ). A previous study found that the expression of SESN2 was positively associated with the IC50 of sorafenib in HCC cell lines and Sestrin 2 could induce sorafenib primary resistance by activation of the AKT and AMPK pathways ( Dai et al, 2018 ).…”

Section: Sorafenib Resistancementioning

confidence: 99%

Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights

et al. 2022

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Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.

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“…Sestrin (SESN) is a highly conserved protein encoded by genes whose cell expression is up-regulated when exposed to DNA damage, oxidative stress and hypoxia (Qu et al, 2021). It includes three isoforms: SESN1, SESN2, and SESN3 (Lee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…; SESN2 activates the AMPK pathway and inhibits downstream mTORC1-P70S6K to promote autophagy (Peng et al, 2014;Wolfson et al, 2016). Similar to autophagy, the role of SESN2 in tumors is paradoxical (Qu et al, 2021). Some studies have found that SESN2 is a tumor suppressor gene, such as neuroblastoma (Ambrosio et al, 2017), bladder cancer (Liang et al, 2016), colorectal cancer (Wei et al, 2015), and endometrial cancer (Shin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

Huang

et al. 2022

Front. Pharmacol.

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Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway.

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A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis

Cited by 16 publications

References 92 publications

Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes

Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes

Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights

Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

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