Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment

Hasaya Dokduang, Sirinun Juntana, Anchalee Techasen, Nisana Namwat, Puangrat Yongvanit, Narong Khuntikeo, Gregory J. Riggins, Watcharin Loilome

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3519-3528
Number of pages10
JournalTumor Biology
Volume34
Issue number6
DOIs
StatePublished - Dec 1 2013

Keywords

  • Cholangiocarcinoma
  • Kinase inhibitors
  • Protein kinases
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research

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  • Cite this

    Dokduang, H., Juntana, S., Techasen, A., Namwat, N., Yongvanit, P., Khuntikeo, N., Riggins, G. J., & Loilome, W. (2013). Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment. Tumor Biology, 34(6), 3519-3528. https://doi.org/10.1007/s13277-013-0930-9