NDLI: Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment

Content Provider	Springer Nature Link
Author	Dokduang, Hasaya Juntana, Sirinun Techasen, Anchalee Namwat, Nisana Yongvanit, Puangrat Khuntikeo, Narong Riggins, Gregory J. Loilome, Watcharin
Copyright Year	2013
Abstract	Improving therapy for patients with cholangiocarcinoma (CCA) presents a significant challenge. This is made more difficult by a lack of a clear understanding of potential molecular targets, such as deregulated kinases. In this work, we profiled the activated kinases in CCA in order to apply them as the targets for CCA therapy. Human phospho-receptor tyrosine kinases (RTKs) and phospho-kinase array analyses revealed that multiple kinases are activated in both CCA cell lines and human CCA tissues that included cell growth, apoptosis, cell to cell interaction, movement, and angiogenesis RTKs. Predominately, the kinases activated downstream were those in the PI3K/Akt, Ras/MAPK, JAK/STAT, and Wnt/β-catenin signaling pathways. Western blot analysis confirms that Erk1/2 and Akt activation were increased in CCA tissues when compared with their normal adjacent tissue. The inhibition of kinase activation using multi-targeted kinase inhibitors, sorafenib and sunitinib led to significant cell growth inhibition and apoptosis induction via suppression of Erk1/2 and Akt activation, whereas drugs with specificity to a single kinase showed less potency. In conclusion, our study reveals the involvement of multiple kinase proteins in CCA growth that might serve as therapeutic targets for combined kinase inhibition.
Starting Page	3519
Ending Page	3528
Page Count	10
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	34
Issue Number	6
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-06-29
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Protein kinases Receptor tyrosine kinase Kinase inhibitors Cholangiocarcinoma Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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