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Calcium signalling in progression of Groups 3 and 4 medulloblastomas [Poster]

Citation

Azimi, I, Calcium signalling in progression of Groups 3 and 4 medulloblastomas [Poster], 31st Lorne Cancer Conference, 14-16 February 2019, Lorne, Victoria, Australia (2019) [Conference Extract]


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Official URL: http://cancer-2019.p.asnevents.com.au/days/2019-02...

Abstract

Brain tumours are the leading cause of cancer-related death in children and medulloblastoma (MB) is the most common malignant childhood brain tumour. MB contains four molecular subgroups of WNT, SHH, Group3 and Group4. Groups 3 and 4 (accounting for >60% of all MBs) are associated with high metastasis and poor patient survival rate of around 60%. Due to the harsh nature of current treatments (surgery, radio/chemotherapy), children who even survive the cancer often show severely permanent impaired physical and cognitive function. There is therefore a clear need for new treatment options for these aggressive MBs. Calcium ion (Ca2+) is an intracellular messenger involved in a variety of cellular processes from gene expression to cell growth and death. In addition to its physiological roles, Ca2+ signalling has been widely implicated in several pathological conditions including cancer. Indeed, A variety of the cancer hallmarks such as proliferation, angiogenesis and metastasis are regulated by calcium signalling. The plethora of calcium channels and pumps in the human genome allows nuanced and localised changes in Ca2+ signalling for the specific regulation of cellular processes including cancer hallmarks. This is often accompanied by a remodelling in the level and/or activity of specific Ca2+ transporters in cancer cells. Indeed our in-silico patient data analysis revealed overexpression of specific Ca2+ channels in Groups 3 and 4 MB and their expression correlation with metastasis and patient survival rates. In-vitro analysis of a member of the transient receptor potential (TRP) channels (as one of the identified transporters from the in-silico analysis), demonstrated its upregulation in MB cell lines corresponding to Groups 3 and 4. Pharmacological inhibition of this channel, concentration dependently inhibited proliferation of Group3 D341 cells and sphere formation of Group4 CHLA-01R-MED cells. Further studies are warranted to understand the role of this targetable plasma membrane channel in MB and the potential of its targeting for the control of MB progression and metastasis.

Item Details

Item Type:Conference Extract
Keywords:calcium, medulloblastoma brain cancer
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:151234
Year Published:2019
Deposited By:Pharmacy
Deposited On:2022-07-25
Last Modified:2022-07-28
Downloads:0

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