Potassium and Chloride Ion Channels in Cancer: A Novel Paradigm for Cancer Therapeutics

Banderali, Umberto; Leanza, Luigi; Eskandari, Najmeh; Gentile, Sandro

doi:10.1007/112_2021_62

Cited by 7 publications

(5 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study demonstrated the critical role of TTYH3 in promoting CRC metastasis and in regulating EMT‐related molecules expression. Although previous research has suggested that chloride channels are linked to the progression of malignant tumors 28 . Interestingly, our findings indicate that the TTYH3‐mediated facilitation of CRC cell migration is not reliant on the functionality of chloride ion channels.…”

Section: Discussioncontrasting

confidence: 49%

“…Although previous research has suggested that chloride channels are linked to the progression of malignant tumors. 28 Interestingly, our findings indicate that the TTYH3-mediated facilitation of CRC cell migration is not reliant on the functionality of chloride ion channels. This is supported by the absence of any observed effects when cells was exposed to a specific channel blocker or treated by the ion channel activity mutant plasmids.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7

Lu,

Deng,

Liu

et al. 2024

MedComm

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the leading cancers worldwide, with metastasis being a major cause of high mortality rates among patients. In this study, dysregulated gene Tweety homolog 3 (TTYH3) was identified by Gene Expression Omnibus database. Public databases were used to predict potential competing endogenous RNAs (ceRNAs) for TTYH3. Quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry were utilized to analyze TTYH3 and histone deacetylase 7 (HDAC7) levels. Luciferase assays confirmed miR‐1271‐5p directly targeting the 3′ untranslated regions of TTYH3 and HDAC7. In vitro experiments such as transwell and human umbilical vein endothelial cell tube formation, as well as in vivo mouse models, were conducted to assess the biological functions of TTYH3 and HDAC7. We discovered that upregulation of TTYH3 in CRC promotes cell migration by affecting the Epithelial–mesenchymal transition pathway, which was independent of its ion channel activity. Mechanistically, TTYH3 and HDAC7 functioned as ceRNAs, reciprocally regulating each other's expression. TTYH3 competes for binding miR‐1271‐5p, increasing HDAC7 expression, facilitating CRC metastasis and angiogenesis. This study reveals the critical role of TTYH3 in promoting CRC metastasis through ceRNA crosstalk, offering new insights into potential therapeutic targets for clinical intervention.

show abstract

Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 68%

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7

Lu,

Deng,

Liu

et al. 2024

MedComm

View full text Add to dashboard Cite

show abstract

“…This is somewhat surprising given the promise such a selective heteroditopic ion-pair receptor would act as a therapeutic for diseases associated with the misregulation of protein ion channels and as an anticancer agent. 70 − 72 …”

Section: Introductionmentioning

confidence: 99%

“…The selective recognition of potassium chloride, however, is, to the best of our knowledge, unprecedented. This is somewhat surprising given the promise such a selective heteroditopic ion-pair receptor would act as a therapeutic for diseases associated with the misregulation of protein ion channels and as an anticancer agent. − …”

Section: Introductionmentioning

confidence: 99%

Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor

et al. 2022

View full text Add to dashboard Cite

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M + (M + = K + , Rb + , Cs + ) sandwich complex and bidentate ChB···X – formation. Extensive quantitative 1 H NMR ion-pair affinity titration experiments, solid–liquid and liquid–liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor’s ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation–anion ion-pair binding observations for halides and oxoanions.

show abstract

“…Ion channels mediate the movement of ions across cellular membranes and play important roles in the development and progression of several human diseases [1][2][3][4]. Channel proteins are complex structures consisting of a central ion-selective pore and various interacting proteins.…”

Section: Introductionmentioning

confidence: 99%

Interactomic exploration of LRRC8A in volume-regulated anion channels

Carpanese,

Festa,

Prosdocimi

et al. 2024

Cell Death Discov.

View full text Add to dashboard Cite

Ion channels are critical in enabling ion movement into and within cells and are important targets for pharmacological interventions in different human diseases. In addition to their ion transport abilities, ion channels interact with signalling and scaffolding proteins, which affects their function, cellular positioning, and links to intracellular signalling pathways. The study of “channelosomes” within cells has the potential to uncover their involvement in human diseases, although this field of research is still emerging. LRRC8A is the gene that encodes a crucial protein involved in the formation of volume-regulated anion channels (VRACs). Some studies suggest that LRRC8A could be a valuable prognostic tool in different types of cancer, serving as a biomarker for predicting patients’ outcomes. LRRC8A expression levels might be linked to tumour progression, metastasis, and treatment response, although its implications in different cancer types can be varied. Here, publicly accessible databases of cancer patients were systematically analysed to determine if a correlation between VRAC channel expression and survival rate exists across distinct cancer types. Moreover, we re-evaluated the impact of LRRC8A on cellular proliferation and migration in colon cancer via HCT116 LRRC8A-KO cells, which is a current topic of debate in the literature. In addition, to investigate the role of LRRC8A in cellular signalling, we conducted biotin proximity-dependent identification (BioID) analysis, revealing a correlation between VRAC channels and cell-cell junctions, mechanisms that govern cellular calcium homeostasis, kinases, and GTPase signalling. Overall, this dataset improves our understanding of LRRC8A/VRAC and explores new research avenues while identifying promising therapeutic targets and promoting inventive methods for disease treatment.

show abstract

Potassium and Chloride Ion Channels in Cancer: A Novel Paradigm for Cancer Therapeutics

Cited by 7 publications

References 121 publications

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7

Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor

Interactomic exploration of LRRC8A in volume-regulated anion channels

Contact Info

Product

Resources

About