Interplay of CRAC channels with Ca2+ activated K+ channels

Changes in intra- and extracellular ion concentrations are essential in cellular processes and biological functions. Ions are transported across certain pores, the so-called ion channels, within the cell membrane. In this project we aim to improve the understanding how two types of ion channels, a calcium (Ca2+) and a potassium (K+) selective one, interplay with each other and trigger prostate and colon cancer cell growth. A unique Ca2+ entry pathway into living cells represents the so-called Ca2+ release-activated Ca2+ (CRAC) ion channel. Ca2+ entry across this ion pore into the cell regulates a huge diversity of proteins including also Ca2+ activated K+ channels. Defects in those channels or their altered appearance in the human cell can cause among diverse diseases also the development of cancer, highlighting the clinical relevance of those ion pores. Specifically, an interplay of these types of ion channels has been shown to trigger breast, colon and prostate cancer cell growth. However, the detailed molecular determinants underlying the reported co- regulation of Ca2+ and K+ channels have so far remained unresolved and thus, will be clarified throughout this project. For that a combined approach of functional, fluorescence and biochemical studies will be employed to uncover key sites mediating the interplay of those ion channels. Whether a suppression of such key regions impairs the co-regulation of the respective ion channels and in consequence also cancer cell growth will be further investigated. In summary these studies will contribute for to a better understanding of molecular factors contributing to prostate and colon cancer cell growth and provide the basis for the development of novel therapeutic approaches.

Changes in intra- and extracellular ion concentrations are essential in cellular processes and biological functions. Ions are transported across certain pores, the so-called ion channels, within the cell membrane. In this project we aim to improve the understanding how two types of ion channels, a calcium (Ca2+) and a potassium (K+) selective one, interplay with each other and trigger prostate cancer cell growth. A unique Ca2+ entry pathway into living cells represents the so-called Ca2+ release-activated Ca2+ (CRAC) ion channel. Ca2+ entry across this ion pore into the cell regulates a huge diversity of proteins including also Ca2+ activated K+ channels. Defects in those channels or their altered appearance in the human cell can cause among diverse diseases also the development of cancer, highlighting the clinical relevance of those ion pores. Specifically, an interplay of these types of ion channels has been shown to trigger breast, colon and prostate cancer cell growth. However, the detailed molecular conditions for the interaction of these ion channels were unknown until the start of this project. Critical regions and factors that are important for the co-regulation of these ion pores were identified as part of this project. To this end, functional, fluorescence microscopic and biochemical analyses were carried out. Furthermore, it was shown that the interaction of these ion pores is involved in the growth of prostate cancer cells. In summary, our studies will contribute to a better understanding of the molecular factors that contribute to the development of prostate cancer and provide a basis for the development of new therapeutic approaches.