Skip to main content Accessibility help
×
Home

CNSS Chair’s Select Abstract Presentations: Developmental phosphoproteomics identifies Casein Kinase 2 as a therapeutic target in medulloblastoma

  • T Purzner (a1), J Purzner (a1), Y Cho (a2), J Elias (a2) and M Scott (a3)...

Abstract

Background: The hedgehog pathway (Hh) is an important developmental signaling pathway that is commonly dysregulated in brain tumors, most notably in medulloblastomas. To identify novel therapeutic targets within the Hh pathway, we performed the first quantitative proteome-wide evaluation of phosphorylation events resulting from in vitro SHH administration and occurring throughout Hh-driven cerebellar development in vivo. Methods: Multiplexed quantitative mass spectrometry was done using Tandem Mass Tags 10-plex reagents, TiO2 phosphopeptide enrichment and HPLC-MS/MS/MS. Results: Motif analysis of 2-fold changing phosphorylation events suggested casein kinase 2 (CK2) was responsible for mediating 45% of all changes in phosphorylation. Epistasis studies revealed that CK2 activity is necessary for hedgehog signaling and affects terminal signaling components, thereby circumventing challenges of emergence of resistance and a priori resistance that are commonly encountered with existing small molecule inhibitors in medulloblastoma. In vivo, mice harboring MB allografts resistant to current therapies showed near-complete cessation of tumor growth in response to a CK2 inhibitor. Conclusion: Our use of developmental phosphoproteomics revealed casein kinase 2 as a key regulator of hedgehog signaling and therapeutic target in medulloblastoma. Our success establishes a foundation for us, and others, to apply a similar approach in different tumor initiating pathways.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      CNSS Chair’s Select Abstract Presentations
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      CNSS Chair’s Select Abstract Presentations
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      CNSS Chair’s Select Abstract Presentations
      Available formats
      ×

Copyright

CNSS Chair’s Select Abstract Presentations: Developmental phosphoproteomics identifies Casein Kinase 2 as a therapeutic target in medulloblastoma

  • T Purzner (a1), J Purzner (a1), Y Cho (a2), J Elias (a2) and M Scott (a3)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed