The expression and survival significance of sodium glucose transporters in pancreatic cancer

Du, Jiali; Gu, Jichun; Deng, Jixin; Kong, Lei; Guo, Yujie; Jin, Chen; Bao, Yun; Fu, Deliang; Li, Ji

doi:10.1186/s12885-021-09060-4

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…The promising findings in the field of cardiometabolic medicine set the stage for future research to explore whether the benefits of gliflozins can expand to inpatients with non-cardiometabolic disorders. Considering encouraging preclinical data [ 48 , 49 ] and the wealth of mechanisms of action of these drugs, these could include, but are not restricted to, sepsis, cirrhotic ascites, and malignancies.…”

Section: Discussionmentioning

confidence: 99%

From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

Koufakis

Mustafa

Ajjan

et al. 2022

Drugs

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The management of hyperglycemia in patients admitted to hospital is mainly based on insulin therapy. However, the positive and rapid effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes raises the possibility that they might confer benefits to hospitalized patients. In recent, well designed, randomized trials (SOLOIST-WHF and EMPULSE) recruiting inpatients with heart failure (HF), SGLT2i demonstrated the potential to improve survival and quality of life and reduce the number of HF events, time to first HF event, hospitalizations, and urgent visits for HF compared with placebo. They were also well tolerated, whereas incidence of diabetic ketoacidosis was low. In EMBODY, empagliflozin was shown to be protective against the deleterious effects of cardiac injury in patients with acute myocardial infarction. In DARE-19, the administration of dapagliflozin to inpatients with cardiometabolic risk factors and COVID-19 was based on the hypothesis that the anti-inflammatory properties of SGLT2i could alleviate organ damage. Although the findings did not reach statistical significance, the efficacy and safety profiles of the drug were encouraging. These promising findings in the field of cardiometabolic medicine set the stage for future research to explore whether the benefits of gliflozins can expand to inpatients with non-cardiometabolic disorders, including sepsis, cirrhotic ascites, and malignancies. The concept of inpatient use of SGLT2i has evolved greatly over the past few years. The latest evidence suggests that SGLT2i may be effective and safe in the hospital setting, provided patients are carefully selected and closely monitored. Real-world data will prove whether present hope about inpatient use of gliflozins will transform into future confidence.

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Section: Discussionmentioning

confidence: 99%

From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

Koufakis

Mustafa

Ajjan

et al. 2022

Drugs

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“…Expression of KLF4 and predicted target genes in CC patients was analyzed using TCGA-COAD database (T (tumor) = 275; N (normal) = 349) by ‘R’ (version 4.1.1) 19 language from TCGA website ( https://portal.gdc.cancer.gov/ ) 20 . Survival analysis were carried out using the ‘survival’ package 21 .…”

Section: Methodsmentioning

confidence: 99%

KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer

Zheng

Chen

et al. 2023

Cancer Biology & Therapy

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Background Accumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis. We investigated how Kruppel-like factor 4 (KLF4) affected 5-FU resistance and autophagy in CC cells. Methods KLF4 expression and its downstream target gene RAB26 in CC tissues was analyzed by bioinformatics analysis, and the effect of abnormal KLF4 expression on prognoses of CC patients was predicted. Luciferase reporter assay detected the targeted relationship between KLF4 and RAB26. The viability and apoptosis of CC cells were analyzed by CCK-8 and flow cytometry. The formation of intracellular autophagosomes was detected by confocal laser scanning microscopy and immunofluorescence staining. The mRNA and protein levels were assayed by qRT-PCR and western blot. A xenograft animal model was constructed to verify the function of KLF4. Rescue assay was employed to verify whether KLF4/RAB26 could affect 5-FU resistance in CC cells through autophagy. Results KLF4 and RAB26 were lowly expressed in CC. KLF4 correlated with patients’ survival. KLF4 was down-regulated in 5-FU resistant CC cells. KLF4 overexpression suppressed the proliferation and 5-FU resistance of CC cells, and inhibited LC3 II/I expression and autophagosome formation. Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance. In vivo assay verified that KLF4 inhibited 5-FU resistance in CC cells. Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU. Conclusion KLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.

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“…Analysis of data in the Gene Expression Omnibus data base (GEO) and Oncomine databases have revealed comparable findings. However, no significant expression has been observed for SGLT2 (40). SWEETs, a novel glucose transporter encoded by SLC50, was first discovered in 2010 by Chen et al (41).…”

Section: Overexpression Of Glucose Transportermentioning

confidence: 99%

Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression

Dong

et al. 2022

Front. Immunol.

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Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.

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The expression and survival significance of sodium glucose transporters in pancreatic cancer

Cited by 6 publications

References 46 publications

From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer

Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression

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