Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review)

Zhang, Guoan; Hou, Sen; Li, Shuyue; Wang, Yequan; Cui, Wen

doi:10.3892/ijo.2024.5636

Cited by 5 publications

(2 citation statements)

References 249 publications

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“…In parallel, NR exposure led to decreased abundance of proteins involved in the folding, aggregation, or turnover of proteins, in l -serine biosynthesis, mRNA transcription, posttranscriptional gene silencing, double-strand break repair, and regulation of protein phosphorylation (Figures c, , S5 and Table S6). Among the 12 downregulated proteins described here, 11 have been shown to be upregulated in different types of cancer. − Downregulation of these proteins may have a role in slowing the growth and inducing apoptosis of the NR exposed cells, despite the shift to glycolytic metabolism. To the best of our knowledge, this is the first report showing the modulation of the abundance of the described sets of proteins by NR exposure.…”

Section: Discussionmentioning

confidence: 93%

“…Except for cellular tumor antigen p53 (TP53), the other 11 proteins have been shown to be upregulated in different types of cancer (Table S6). − Six of these proteins are involved in the folding, aggregation, or turnover of proteins [hypoxia up-regulated protein 1 (HYOU1), heat shock 70 kDa protein 1A or 1B (HSPA1A or 1B), protein disulfide-isomerase (P4HB), prolyl 4-hydroxylase subunit alpha-2 (P4HA2), serpin H1 (SERPINH1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1)]. Two are involved in l -serine biosynthesis [phosphoserine aminotransferase (PSAT1), phosphoserine phosphatase (PSPH)].…”

Section: Resultsmentioning

confidence: 99%

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Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Cordeiro,

Marzola,

Maekawa

et al. 2024

Chem. Res. Toxicol.

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Nicotinamide riboside (NR), a NAD + precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD + availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD + increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.

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Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Cordeiro,

Marzola,

Maekawa

et al. 2024

Chem. Res. Toxicol.

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Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis

Sun,

Pu,

et al. 2024

Preprint

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Background Colorectal cancer (CRC) exhibits a high incidence globally, with the liver being the most common site of distant metastasis. At the time of diagnosis, 20–30% of CRC patients already present with liver metastases. Colorectal liver metastasis (CRLM) is a major cause of mortality among CRC patients. The pathogenesis of CRLM involves complex molecular mechanisms and the hepatic immune microenvironment, but current clinical prevention and treatment are significantly limited. Recent studies have revealed that the major facilitator superfamily domain containing protein-2a (Mfsd2a) plays a pivotal role in the development and metastasis of various cancers.. For instance, Mfsd2a inhibits gastric cancer initiation and progression and may impact angiogenesis. However, the mechanisms by which Mfsd2a influences CRC progression and liver metastasis remain unclear. Methods In this study, we conducted a survival analysis of Mfsd2a in colorectal cancer using data from the GEPIA and GEO databases, and examined the expression differences between primary tumor (PT) and liver metastasis (LM). We further assessed the clinical significance and prognostic relevance of Mfsd2a through immunohistochemical analysis of tissue samples from 70 CRLM patients. Moreover, Kaplan-Meier analysis was used to perform survival analysis on these patients. The biological function of Mfsd2a in CRLM was confirmed by a series of experiments conducted both in vitro and in vivo. Additionally, we investigated downstream molecular pathways using western blot, co- immunoprecipitation, immunofluorescence, and mass spectrometry techniques. Results We observed that Mfsd2a expression is reduced in LM compared to PT, and higher Mfsd2a levels are associated with better prognosis in CRLM patients. Furthermore, function assays demonstrated that Mfsd2a suppresses CRC cells proliferation, migration, invasion, and EMT in vitro, while also delaying tumor growth and liver metastasis in vivo. Mechanistically, Mfsd2a interacts with S100A14, enhancing its expression and inhibiting phosphorylation of STAT3. In addition, the STAT3 activator colivelin partially reversed the inhibitory effect of Mfsd2a overexpression on the progression of colorectal cancer and liver metastasis. Conclusion In summary, Mfsd2a inhibits colorectal cancer progression and liver metastasis by interacting with S100A14, thereby suppressing the phosphorylation of STAT3. Mfsd2a functions as a tumor suppressor in CRLM and could be a promising therapeutic target for treating CRC patients with liver metastasis.

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Anti-Cancer Potential of Isoflavone-Enriched Fraction from Traditional Thai Fermented Soybean against Hela Cervical Cancer Cells

Sukhamwang,

Inthanon,

Dejkriengkraikul

et al. 2024

IJMS

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Cervical cancer is a leading cause of gynecological malignancies and cancer-related deaths among women worldwide. This study investigates the anti-cancer activity of Thua Nao, a Thai fermented soybean, against HeLa cervical carcinoma cells, and explores its underlying mechanisms. Our findings reveal that the ethyl acetate fraction of Thua Nao (TN-EA) exhibits strong anti-cancer potential against HeLa cells. High-performance liquid chromatography (HPLC) analysis identified genistein and daidzein as the major isoflavones in TN-EA responsible for its anti-cancer activity. TN-EA and genistein reduced cell proliferation and induced G2/M phase arrest, while daidzein induced G1 arrest. These responses were associated with the downregulation of cell cycle regulators, including Cyclin B1, cycle 25C (Cdc25C), and phosphorylated cyclin-dependent kinase 1 (CDK-1), and the upregulation of the cell cycle inhibitor p21. Moreover, TN-EA and its active isoflavones promoted apoptosis in HeLa cells through the intrinsic pathway, evidenced by increased levels of cleaved Poly (ADP-ribose) polymerase (PARP) and caspase-3, loss of mitochondrial membrane potential, and the downregulation of anti-apoptotic proteins B-cell leukemia/lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xL), cellular inhibitor of apoptosis proteins 1 (cIAP), and survivin. Additionally, TN-EA and its active isoflavones effectively reduced cell invasion and migration by downregulating extracellular matrix degradation enzymes, including Membrane type 1-matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR), and reduced the levels of the mesenchymal marker N-cadherin. At the molecular level, TN-EA suppressed STAT3 activation via the regulation of JNK and Erk1/2 signaling pathways, leading to reduced proliferation and invasion of HeLa cells.

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Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review)

Cited by 5 publications

References 249 publications

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis

Anti-Cancer Potential of Isoflavone-Enriched Fraction from Traditional Thai Fermented Soybean against Hela Cervical Cancer Cells

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