Inorganic phosphate transporters in cancer: Functions, molecular mechanisms and possible clinical applications

Lacerda-Abreu, Marco Antônio; Russo‐Abrahão, Thais; Monteiro, Robson Q.; Rumjanek, Franklin David; Meyer‐Fernandes, José Roberto

doi:10.1016/j.bbcan.2018.05.001

Cited by 27 publications

(39 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, P i has recently been implicated in cancer aggressiveness [ 369 ]. SLC20A1 may be overexpressed in tongue tumors [ 370 , 371 ], and Npt2b expression is increased in lung cancers [ 369 , 371 ]. Furthermore, high dietary P i stimulates the AKT-mammalian target of rapamycin regulatory pathway, leading to higher lung cancer aggressiveness in K- ras LA1 mice [ 369 , 371 ].…”

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

“…SLC20A1 may be overexpressed in tongue tumors [ 370 , 371 ], and Npt2b expression is increased in lung cancers [ 369 , 371 ]. Furthermore, high dietary P i stimulates the AKT-mammalian target of rapamycin regulatory pathway, leading to higher lung cancer aggressiveness in K- ras LA1 mice [ 369 , 371 ]. The knockdown of Npt2b with siRNA was shown to decrease the number and size of lung tumors in this mouse model, suggesting that the regulation of P i consumption through NPT2b knockdown may be a possible treatment for lung cancer [ 371 , 372 ].…”

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

“…Furthermore, high dietary P i stimulates the AKT-mammalian target of rapamycin regulatory pathway, leading to higher lung cancer aggressiveness in K- ras LA1 mice [ 369 , 371 ]. The knockdown of Npt2b with siRNA was shown to decrease the number and size of lung tumors in this mouse model, suggesting that the regulation of P i consumption through NPT2b knockdown may be a possible treatment for lung cancer [ 371 , 372 ]. Similarly, a high P i concentration in the tumor microenvironment has been identified as a marker for tumor progression in mouse mammary gland tumors [ 371 , 373 ].…”

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

See 2 more Smart Citations

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Serna

Bergwitz

2020

Nutrients

View full text Add to dashboard Cite

Inorganic phosphate (Pi) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. Pi is the main source of dietary phosphorus. Reduced bioavailability of Pi or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about Pi sensing, and endocrine regulation of Pi levels. Moreover, we also examine the roles of Pi in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.

show abstract

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

Section: Importance Of Dietary Phosphorus For Healthy Agingmentioning

confidence: 99%

See 1 more Smart Citation

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Serna

Bergwitz

2020

Nutrients

View full text Add to dashboard Cite

show abstract

“…Studies dating from the 1980s have suggested that NaPi-IIb can be used as a marker for specific tumors including ovarian and lung cancer, although the identity of NaPi-IIb as the marker was initially unknown (reviewed in [59]). A monoclonal antibody was developed to identify epithelial tumors through binding to an antigen named MX35, which on further characterization was found to be NaPi-IIb [63].…”

Section: Napi-iib and Cancermentioning

confidence: 99%

“…In the tumors expressing NaPi-IIb, the protein has been identified as wild type; however, a recent phenomenon whereby SLC34A2 undergoes molecular re-arrangement with ROS-1, a tyrosine kinase receptor, to create a constitutively active tyrosine kinase that increases oncogenicity has been described [45,16]. Furthermore, there is some evidence that high expression of NaPi-IIb may confer resistance to cancer chemotherapy and may increase metastatic potential [59].…”

Section: Napi-iib and Cancermentioning

confidence: 99%

Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: mutations and disease associations

Lederer

Wagner

2018

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

The Na-dependent phosphate transporter NaPi-IIa (SLC34A1) is mostly expressed in kidney, whereas NaPi-IIb (SLC34A2) has a wider tissue distribution with prominent expression in the lung and small intestine. NaPi-IIa is involved in renal reabsorption of inorganic phosphate (Pi) from urine, and patients with biallelic inactivating mutations in SLC34A1 develop hypophosphatemia, hypercalcemia, hypercalciuria and nephrocalcinosis, and nephrolithiasis in early childhood. Monoallelic mutations are frequent in the general population and may impact on the risk to develop kidney stones in adulthood. SNPs in close vicinity to the SLC34A1 locus associate with the risk to develop CKD. NaPi-IIb mediates high-affinity transport of Pi from the diet and appears to be mostly important during low Pi availability. Biallelic inactivating SLC34A2 mutations are found in patients with pulmonary alveolar microlithiasis, a lung disease characterized by the deposition of microcrystals. In contrast, no evidence for disturbed systemic Pi homeostasis has been reported in these patients to date. Nevertheless, NaPi-IIb-mediated intestinal Pi absorption may be a target for pharmaceutical interventions in patients with chronic kidney disease and Pi overload.

show abstract

Optimization of a modeling platform to predict oncogenes from genome‐scale metabolic networks of non‐small‐cell lung cancers

et al. 2021

View full text Add to dashboard Cite

Cancer cell dysregulations result in the abnormal regulation of cellular metabolic pathways.By simulating this metabolic reprogramming using constraint-based modeling approaches, oncogenes can be predicted, and this knowledge can be used in prognosis and treatment. We introduced a trilevel optimization problem describing metabolic reprogramming for inferring oncogenes. First, this study used RNA-Seq expression data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) samples and their healthy counterparts to reconstruct tissue-specific genome-scale metabolic models and subsequently build the flux distribution pattern that provided a measure for the oncogene inference optimization problem for determining tumorigenesis. The platform detected 45 genes for LUAD and 84 genes for LUSC that lead to tumorigenesis. A high level of differentially expressed genes was not an essential factor for determining tumorigenesis. The platform indicated that pyruvate kinase (PKM), a well-known oncogene with a low level of differential gene expression in LUAD and LUSC, had the highest fitness among the predicted oncogenes based on computation. By contrast, pyruvate kinase L/R (PKLR), an isozyme of PKM, had a high level of differential gene expression in both cancers.

show abstract

Inorganic phosphate transporters in cancer: Functions, molecular mechanisms and possible clinical applications

Cited by 27 publications

References 48 publications

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: mutations and disease associations

Optimization of a modeling platform to predict oncogenes from genome‐scale metabolic networks of non‐small‐cell lung cancers

Contact Info

Product

Resources

About