Emerging roles of the solute carrier family in pancreatic cancer

Wu, Zijian; Xu, Jin; Chen, Liang; Meng, Qingcai; Hua, Jie; Wang, Wei; Zhang, Bo; Liu, Jiang; Yu, Xianjun; Shi, Si

doi:10.1002/ctm2.356

Cited by 29 publications

(25 citation statements)

References 123 publications

(302 reference statements)

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“…Solute carriers (SLCs) in the cell membrane are responsible for mediating the influx of nutrients and drugs. In cancer cells, however, SLC transporters are expressed differently than in normal cells [ 23 , 24 , 25 , 26 ]. Therefore, it is important to consider the expression pattern of SLC transporters in chemotherapy.…”

Section: Multidrug Resistance In Cancer Chemotherapymentioning

confidence: 99%

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Kim

Park

Lee

2021

Cancers

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Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism of MDR. Recent studies have suggested that nitric oxide (NO) can be used to overcome MDR by inhibiting the ATPase function of ATP-dependent pumps. Several attempts have been made to deliver NO to the tumor microenvironment (TME), however there are limitations in delivery. Glycyrrhizin (GL), an active compound of licorice, has been reported to both reduce the MDR effect by inhibiting ATP-dependent pumps and function as a regulator of NO production in the TME. In this review, we describe the potential role of GL as an NO regulator and MDR inhibitor that efficiently reduces the MDR effect in cancer chemotherapy.

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Section: Multidrug Resistance In Cancer Chemotherapymentioning

confidence: 99%

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Kim

Park

Lee

2021

Cancers

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“…In fact, cancer cells present plasticity and adaptative capacity in response to microenvironment alterations to continue to proliferate and adapt to dynamic changes, the amino acid (AA) bioavailability being an important necessity to answer the high demand of nutrients during the cancer progression [ 9 ]. Thus, solute carriers’ transporters (SLCs) present a key role in CRC progression, since these transmembrane carriers are involved in the transport of several solutes such as AA, lipids and inorganic solutes, participating in key carcinogenesis processes, such as proliferation, apoptosis, invasion and metastases formation [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype

Almeida

Teixeira

Dias

et al. 2022

Biology

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Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients’ prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of LAT1 and ASCT2 mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry LAT1, ASCT2 and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs’ internalization was associated with the increase of LAT1 mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the LAT1-EVs’ mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.

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“…Given the need for transporters if drugs are to cross cell membranes, one can make a virtue of necessity [ 284 ] by seeking either to exploit their natural expression profiles [ 291 , 292 , 293 ] or to vary them explicitly [ 294 ], so as to target them to particular tissues [ 295 ]. The latter has obvious benefits in oncology [ 296 , 297 , 298 , 299 , 300 ], where the necessary cytotoxicity of many drugs, such as nucleoside analogues, is rather non-specific. The strategy can be used for modifying both influx and efflux transporters, though the latter is likely to prove more efficacious [ 276 ].…”

Section: Introductionmentioning

confidence: 99%

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Kell

2021

Molecules

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Over the years, my colleagues and I have come to realise that the likelihood of pharmaceutical drugs being able to diffuse through whatever unhindered phospholipid bilayer may exist in intact biological membranes in vivo is vanishingly low. This is because (i) most real biomembranes are mostly protein, not lipid, (ii) unlike purely lipid bilayers that can form transient aqueous channels, the high concentrations of proteins serve to stop such activity, (iii) natural evolution long ago selected against transport methods that just let any undesirable products enter a cell, (iv) transporters have now been identified for all kinds of molecules (even water) that were once thought not to require them, (v) many experiments show a massive variation in the uptake of drugs between different cells, tissues, and organisms, that cannot be explained if lipid bilayer transport is significant or if efflux were the only differentiator, and (vi) many experiments that manipulate the expression level of individual transporters as an independent variable demonstrate their role in drug and nutrient uptake (including in cytotoxicity or adverse drug reactions). This makes such transporters valuable both as a means of targeting drugs (not least anti-infectives) to selected cells or tissues and also as drug targets. The same considerations apply to the exploitation of substrate uptake and product efflux transporters in biotechnology. We are also beginning to recognise that transporters are more promiscuous, and antiporter activity is much more widespread, than had been realised, and that such processes are adaptive (i.e., were selected by natural evolution). The purpose of the present review is to summarise the above, and to rehearse and update readers on recent developments. These developments lead us to retain and indeed to strengthen our contention that for transmembrane pharmaceutical drug transport “phospholipid bilayer transport is negligible”.

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Emerging roles of the solute carrier family in pancreatic cancer

Cited by 29 publications

References 123 publications

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

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