Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

Chae, Hee‐Sung; Gil, Minchan; Saha, Subbroto Kumar; Kwak, Hee Jeung; Park, Hwan‐Woo; Vellingiri, Balachandar; Cho, Ssang-Goo

doi:10.3390/jpm10030109

Cited by 19 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sesn2-deficient mouse embryonic fibroblast (MEF) cells were significantly more susceptible to oncogenic stresses (Budanov and Karin, 2008). Sesn2 inhibition promotes A549, human a non-small cell lung carcinoma, cell growth (Sablina et al, 2005), and its expression level is negatively correlated with the lung cancer survival rate (Chae et al, 2020). Sesn3 induces apoptosis of human non-small cell lung cancer (NSCLC) cells in dietary compound cucurbitacin B treatment (Khan et al, 2017).…”

Section: Sestrins In Nutrient Stress-sensing and Metabolic Dysfunctionmentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

show abstract

Section: Sestrins In Nutrient Stress-sensing and Metabolic Dysfunctionmentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, in contrast to this study, Chae et al demonstrated that the expression of sestrin 2 in lung cancer was higher than in normal lung tissue by using the Oncomine and Human Protein Atlas databases. Furthermore, these authors showed that overexpressed sestrin 2 was a marker for poor prognosis in lung cancer by analyzing the PrognoScan database and Kaplan–Meier Plotter [ 44 ]. Additionally, by analyzing data from the Gene Expression Omnibus and Cancer Genome Atlas analysis, Lin et al revealed that the survival time for lung cancer patients with lower sestrin 2 expression was significantly prolonged [ 45 ].…”

Section: The Alteration Of Sestrin 2 Gene Expression In Various Cancersmentioning

confidence: 99%

“…Sestrin 2 also has a potentially oncogenic function in lung cancer. Knockdown of sestrin 2 with shRNA inhibited proliferation, migration, and sphere formation in A549 cells [ 44 ]. In pancreatic cancer, overexpression of sestrin 2 promoted PANC-1 cells proliferation and increased glycolysis, and mTOR inhibitors suppressed these effects in vitro.…”

Section: Promotive Effects Of Sestrin 2 In Cancermentioning

confidence: 99%

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

Luo

Zhang

et al. 2021

Cancer Cell Int

View full text Add to dashboard Cite

Sestrin 2, a highly conserved stress-induced protein, participates in the pathological processes of metabolic and age-related diseases. This p53-inducible protein also regulates cell growth and metabolism, which is closely related to malignant tumorigenesis. Sestrin 2 was reported to regulate various cellular processes, such as tumor cell proliferation, invasion and metastasis, apoptosis, anoikis resistance, and drug resistance. Although sestrin 2 is associated with colorectal, lung, liver, and other cancers, sestrin 2 expression varies among different types of cancer, and the effects and mechanisms of action of this protein are also different. Sestrin 2 was considered a tumor suppressor gene in most studies, whereas conflicting reports considered sestrin 2 an oncogene. Thus, this review aims to examine the literature regarding sestrin 2 in various cancers, summarize its roles in suppression and tumorigenesis, discuss potential mechanisms in the regulation of cancer, and provide a basis for follow-up research and potential cancer treatment development.

show abstract

“…Among sestrin family, Sestrin2 has shown regulating activities in some cancers [14]. Knocking down Sestrin2 in non-small cell lung cancer cells resulted in reduced lung cancer progression [15]. Down-regulation of Sestrin2 promoted cell proliferation, migration, and ROS production in endometrial cancer cells [16].…”

Section: Introductionmentioning

confidence: 99%

Sestrin2 reduces the cancer stemness via the Wnt/β-catenin signaling in colorectal cancer

Wei

Zheng

et al. 2021

Preprint

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women in China. In previous studies, Sestrin2 was demonstrated to have functions in CRC. However, the relationship between Sestrin2 and cancer stemness has not been reported. To investigate the contribution of Sestrin2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas datasets and found that Sestrin2 was downregulated in CRC. Using a lentivirus vector, we verified that Sestrin2 suppressed CRC cell proliferation, migration, and colony formation. Furthermore, sphere formation, flow cytometry, quantitative PCR, and Western blot analysis verified the effect of Sestrin2 on the cancer stem ness, including the expression of cluster of differentiation 44, octamer-binding transcription factor 4, sex-determining region Y-box 2, CXC chemokine receptor 4, and the Wnt pathway downstream factors β-catenin and c-Myc. Consistently, the Wnt pathway activator BML-284 partially rescued the effects of Sestrin2 on the expression of proteins related to the cancer stemness. Furthermore, in a mouse xenoplant model, tumors with Sestrin2 were significantly reduced in size with corresponding changes in the cancer stemness. Collectively, our results suggest that Sestrin2 inhibits CRC cell progression by downregulating the Wnt signaling pathway. Thus, Sestrin2 may be a promising therapeutic target for CRC.

show abstract

Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

Cited by 19 publications

References 45 publications

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

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

Sestrin2 reduces the cancer stemness via the Wnt/β-catenin signaling in colorectal cancer

Contact Info

Product

Resources

About