Crucial role of the pentose phosphate pathway in malignant tumors (Review)

Jin, Lin; Zhou, Yanhong

doi:10.3892/ol.2019.10112

Cited by 118 publications

(135 citation statements)

References 108 publications

(111 reference statements)

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“…Dramatic changes in energy fluxes occur during carcinogenesis as supported by the massively perturbed protein expression profile in breast cancer tissue compared to normal breast tissue ( Figure 3A). Most notably, enzymes of the glycolytic pathway increase substantially ( Figure 3A and Figure S2A) supporting their dominant contribution to supply of energy and chemical components for cell proliferation in cancer tissue [50]. We also see enrichment of the pentose phosphate pathway ( Figure 3A and Figure S2A).…”

Section: Oral Nahco 3 Therapy Does Not Affect Tumor Burden Tumor-frementioning

confidence: 63%

Targeting the Acidic Tumor Microenvironment: Unexpected Pro-Neoplastic Effects of Oral NaHCO3 Therapy in Murine Breast Tissue

Voss

Dreyer

Henningsen

et al. 2020

Cancers

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The acidic tumor microenvironment modifies malignant cell behavior. Here, we study consequences of the microenvironment in breast carcinomas. Beginning at carcinogen-based breast cancer induction, we supply either regular or NaHCO3-containing drinking water to female C57BL/6j mice. We evaluate urine and blood acid-base status, tumor metabolism (microdialysis sampling), and tumor pH (pH-sensitive microelectrodes) in vivo. Based on freshly isolated epithelial organoids from breast carcinomas and normal breast tissue, we assess protein expression (immunoblotting, mass spectrometry), intracellular pH (fluorescence microscopy), and cell proliferation (bromodeoxyuridine incorporation). Oral NaHCO3 therapy increases breast tumor pH in vivo from 6.68 ± 0.04 to 7.04 ± 0.09 and intracellular pH in breast epithelial organoids by ~0.15. Breast tumors develop with median latency of 85.5 ± 8.2 days in NaHCO3-treated mice vs. 82 ± 7.5 days in control mice. Oral NaHCO3 therapy does not affect tumor growth, histopathology or glycolytic metabolism. The capacity for cellular net acid extrusion is increased in NaHCO3-treated mice and correlates negatively with breast tumor latency. Oral NaHCO3 therapy elevates proliferative activity in organoids from breast carcinomas. Changes in protein expression patterns—observed by high-throughput proteomics analyses—between cancer and normal breast tissue and in response to oral NaHCO3 therapy reveal complex influences on metabolism, cytoskeleton, cell-cell and cell-matrix interaction, and cell signaling pathways. We conclude that oral NaHCO3 therapy neutralizes the microenvironment of breast carcinomas, elevates the cellular net acid extrusion capacity, and accelerates proliferation without net effect on breast cancer development or tumor growth. We demonstrate unexpected pro-neoplastic consequences of oral NaHCO3 therapy that in breast tissue cancel out previously reported anti-neoplastic effects.

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Section: Oral Nahco 3 Therapy Does Not Affect Tumor Burden Tumor-frementioning

confidence: 63%

Targeting the Acidic Tumor Microenvironment: Unexpected Pro-Neoplastic Effects of Oral NaHCO3 Therapy in Murine Breast Tissue

Voss

Dreyer

Henningsen

et al. 2020

Cancers

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“…Cancer cells use glucose metabolism in order to supply the higher required proliferation rate, and, in particular, PPP is a metabolic pathway used both to synthesize nucleic acids and to maintain the cellular redox state [21,22].…”

Section: Glucose Metabolism and The Pentose Phosphate Pathway In Tumomentioning

confidence: 99%

“…The non-oxidative branch includes various reversible reactions, consisting of the conversion of different glycolytic intermediates such as fructose-6-phosphate (F6P) and glyceraldehyde-3-phosphate (G3P), into pentose phosphate and vice versa [21,22]. The main enzymes involved in non-oxidative PPP are transketolase (TKT) and transaldolase (TALDO).…”

Section: Glucose Metabolism and The Pentose Phosphate Pathway In Tumomentioning

confidence: 99%

The Pentose Phosphate Pathway and Its Involvement in Cisplatin Resistance

Giacomini

Ragazzi

Pasut

et al. 2020

IJMS

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Cisplatin is the first-line treatment for different types of solid tumors, such as ovarian, testicular, bladder, cervical, head and neck, lung, and esophageal cancers. The main problem related to its clinical use is the onset of drug resistance. In the last decades, among the studied molecular mechanisms of cisplatin resistance, metabolic reprogramming has emerged as a possible one. This review focuses on the pentose phosphate pathway (PPP) playing a pivotal role in maintaining the high cell proliferation rate and representing an advantage for cancer cells. In particular, the oxidative branch of PPP plays a role in oxidative stress and seems to be involved in cisplatin resistance. In light of these considerations, it has been demonstrated that overexpression and higher enzymatic activity of different enzymes of both oxidative and non-oxidative branches (such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transketolase) increase cisplatin resistance, and their silencing or combined treatment with cisplatin could restore cisplatin sensitivity. Moreover, drug delivery systems loaded with both PPP inhibitors and cisplatin give the possibility of reaching cancer cells selectively. In conclusion, targeting PPP is becoming a strategy to overcome cisplatin resistance; however, further studies are required to better understand the mechanisms.

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“…Within the primary tumor, it has been shown that PDA cells can engage different mechanisms to regulate the levels of intracellular ROS. These include increased glucose flux through the pentose phosphate pathway (PPP) [73,74] and increased glutamine metabolism [75,76]. Both of these mechanisms result in a net increase in the levels of the reducing equivalent NADPH, which maintains the levels of intracellular reduced glutathione [77].…”

Section: Surviving Oxidative Changes In the Circulation And Distant Pmentioning

confidence: 99%

Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies

Pereira

Chio

2019

Genes

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Pancreatic ductal adenocarcinoma is an extremely aggressive disease with a high metastatic potential. Most patients are diagnosed with metastatic disease, at which the five-year survival rate is only 3%. A better understanding of the mechanisms that drive metastasis is imperative for the development of better therapeutic interventions. Here, we take the reader through our current knowledge of the parameters that support metastatic progression in pancreatic ductal adenocarcinoma, and the experimental models that are at our disposal to study this process. We also describe the advantages and limitations of these models to study the different aspects of metastatic dissemination.

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Crucial role of the pentose phosphate pathway in malignant tumors (Review)

Cited by 118 publications

References 108 publications

Targeting the Acidic Tumor Microenvironment: Unexpected Pro-Neoplastic Effects of Oral NaHCO3 Therapy in Murine Breast Tissue

Targeting the Acidic Tumor Microenvironment: Unexpected Pro-Neoplastic Effects of Oral NaHCO3 Therapy in Murine Breast Tissue

The Pentose Phosphate Pathway and Its Involvement in Cisplatin Resistance

Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies

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