Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons

Pissas, Karolos-Philippos; Schilling, Maria; Tian, Yuemin; Gründer, Stefan

doi:10.1007/s00424-023-02839-3

Cited by 2 publications

(2 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of functional ASIC1a homomers has recently also been reported for DAOY cells, which are derived from the paediatric tumour MB; ASIC2 and ASIC3 were not expressed [ 61 ]. Furthermore, it was found that DAOY cells were resistant to acid-induced cell death and that they expressed low levels of RIPK3, a kinase downstream of RIPK1 in the necroptosis pathway.…”

Section: Asics In Brain Cancer – Increased Migration Vs Increased Cel...mentioning

confidence: 99%

“…Furthermore, it was found that DAOY cells were resistant to acid-induced cell death and that they expressed low levels of RIPK3, a kinase downstream of RIPK1 in the necroptosis pathway. Strikingly, overexpressing RIPK3 in DAOY cells rendered them vulnerable to acid-induced cell death in an ASIC1a-dependent fashion [ 61 ]. Thus, it appears that sustained activation of ASIC1a can, in principle, induce regulated cell death also in MB cells.…”

Section: Asics In Brain Cancer – Increased Migration Vs Increased Cel...mentioning

confidence: 99%

See 1 more Smart Citation

Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?

Gründer,

Vanek,

Pissas

2024

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

It is increasingly appreciated that the acidic microenvironment of a tumour contributes to its evolution and clinical outcomes. However, our understanding of the mechanisms by which tumour cells detect acidosis and the signalling cascades that it induces is still limited. Acid-sensing ion channels (ASICs) are sensitive receptors for protons; therefore, they are also candidates for proton sensors in tumour cells. Although in non-transformed tissue, their expression is mainly restricted to neurons, an increasing number of studies have reported ectopic expression of ASICs not only in brain cancer but also in different carcinomas, such as breast and pancreatic cancer. However, because ASICs are best known as desensitizing ionotropic receptors that mediate rapid but transient signalling, how they trigger intracellular signalling cascades is not well understood. In this review, we introduce the acidic microenvironment of tumours and the functional properties of ASICs, point out some conceptual problems, summarize reported roles of ASICs in different cancers, and highlight open questions on the mechanisms of their action in cancer cells. Finally, we propose guidelines to keep ASIC research in cancer on solid ground.

show abstract

Section: Asics In Brain Cancer – Increased Migration Vs Increased Cel...mentioning

confidence: 99%

Section: Asics In Brain Cancer – Increased Migration Vs Increased Cel...mentioning

confidence: 99%

Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?

Gründer,

Vanek,

Pissas

2024

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

show abstract

Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKCa channels is associated with cell volume changes and cell death under strongly acidic conditions in DAOY medulloblastoma cells

Pissas,

Gründer,

Tian

2024

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Fast growing solid tumors are frequently surrounded by an acidic microenvironment. Tumor cells employ a variety of mechanisms to survive and proliferate under these harsh conditions. In that regard, acid-sensitive membrane receptors constitute a particularly interesting target, since they can affect cellular functions through ion flow and second messenger cascades. Our knowledge of these processes remains sparse, however, especially regarding medulloblastoma, the most common pediatric CNS malignancy. In this study, using RT-qPCR, whole-cell patch clamp, and Ca2+-imaging, we uncovered several ion channels and a G protein-coupled receptor, which were regulated directly or indirectly by low extracellular pH in DAOY and UW228 medulloblastoma cells. Acidification directly activated acid-sensing ion channel 1a (ASIC1a), the proton-activated Cl− channel (PAC, ASOR, or TMEM206), and the proton-activated G protein-coupled receptor OGR1. The resulting Ca2+ signal secondarily activated the large conductance calcium-activated potassium channel (BKCa). Our analyses uncover a complex relationship of these transmembrane proteins in DAOY cells that resulted in cell volume changes and induced cell death under strongly acidic conditions. Collectively, our results suggest that these ion channels in concert with OGR1 may shape the growth and evolution of medulloblastoma cells in their acidic microenvironment.

show abstract

Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons

Cited by 2 publications

References 65 publications

Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?

Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?

Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKCa channels is associated with cell volume changes and cell death under strongly acidic conditions in DAOY medulloblastoma cells

Contact Info

Product

Resources

About