SLC26A9 in airways and intestine: secretion or absorption?

Kunzelmann, Karl; Centeio, Raquel; Ousingsawat, Jiraporn; Talbi, Khaoula; Seidler, Ursula; Schreiber, Rainer

doi:10.1080/19336950.2023.2186434

Cited by 6 publications

(3 citation statements)

References 85 publications

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“…Moreover, another epithelial Cl - channel, CFTR is related to an increased incidence of colon cancer [ 26 – 28 ]. Previous studies showed that CFTR is positive correlation with SLC26A9 in the cystic fibrosis related diseases [ 11 , 29 , 30 ]. However, whether SLC26A9 is implicated in CRC tumorigenesis has never been explored.…”

Section: Discussionmentioning

confidence: 99%

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/β-catenin signaling

Zhang,

Ma,

et al. 2024

Cell Death Discov.

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Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with β-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/β-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the β-catenin inhibitor XAV-939, β-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/β-catenin signaling

Zhang,

Ma,

et al. 2024

Cell Death Discov.

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“…Additionally, in the human lung bronchiolar and alveolar epithelium, SLC26A9 transports Cl − , suggesting that it is a Cl − channel [122,123]. SLC26A9 performs CFTR-like functions in the airways and interacts with CFTR [124].…”

Section: Slc26a6mentioning

confidence: 99%

Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs

Lee,

Hong

2024

IJMS

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Solute carrier family 26 member 4 (SLC26A4) is a member of the SLC26A transporter family and is expressed in various tissues, including the airway epithelium, kidney, thyroid, and tumors. It transports various ions, including bicarbonate, chloride, iodine, and oxalate. As a multiple-ion transporter, SLC26A4 is involved in the maintenance of hearing function, renal function, blood pressure, and hormone and pH regulation. In this review, we have summarized the various functions of SLC26A4 in multiple tissues and organs. Moreover, the relationships between SLC26A4 and other channels, such as cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and sodium chloride cotransporter, are highlighted. Although the modulation of SLC26A4 is critical for recovery from malfunctions of various organs, development of specific inducers or agonists of SLC26A4 remains challenging. This review contributes to providing a better understanding of the role of SLC26A4 and development of therapeutic approaches for the SLC26A4-associated hearing loss and SLC26A4-related dysfunction of various organs.

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“…It will also be interesting to learn to what extent SLC26A9 contributes to airway HCO 3 − secretion when compared to SLC26A4 (pendrin), which probably secretes the most HCO 3 − , particularly during inflammation [28]. In conclusion, the main task of SLC26A9 in the airways and particularly in the alveoli could actually be the reabsorption of Cl − rather than Cl − secretion (reviewed in [144]).…”

Section: Slc26a9 Is Expressed In the Apical Membrane Of Airways From ...mentioning

confidence: 99%

Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins

Kunzelmann,

Ousingsawat,

Kraus

et al. 2023

IJMS

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The Cl−-transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) appear to have more in common than initially suspected, as they all participate in the pathogenic process and clinical outcomes of airway and renal diseases. In the present review, we will therefore concentrate on recent findings concerning electrolyte transport in the airways and kidneys, and the role of CFTR, SLC26A9, and the anoctamins ANO1 and ANO6. Special emphasis will be placed on cystic fibrosis and asthma, as well as renal alkalosis and polycystic kidney disease. In essence, we will summarize recent evidence indicating that CFTR is the only relevant secretory Cl− channel in airways under basal (nonstimulated) conditions and after stimulation by secretagogues. Information is provided on the expressions of ANO1 and ANO6, which are important for the correct expression and function of CFTR. In addition, there is evidence that the Cl− transporter SLC26A9 expressed in the airways may have a reabsorptive rather than a Cl−-secretory function. In the renal collecting ducts, bicarbonate secretion occurs through a synergistic action of CFTR and the Cl−/HCO3− transporter SLC26A4 (pendrin), which is probably supported by ANO1. Finally, in autosomal dominant polycystic kidney disease (ADPKD), the secretory function of CFTR in renal cyst formation may have been overestimated, whereas ANO1 and ANO6 have now been shown to be crucial in ADPKD and therefore represent new pharmacological targets for the treatment of polycystic kidney disease.

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SLC26A9 in airways and intestine: secretion or absorption?

Cited by 6 publications

References 85 publications

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/β-catenin signaling

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/β-catenin signaling

Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs

Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins

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