Calcium calmodulin dependent kinase kinase 2 - A novel therapeutic target for gastric adenocarcinoma

Yashwanth Subbannayya, Nazia Syed, Mustafa A. Barbhuiya, Remya Raja, Arivusudar Marimuthu, Nandini Sahasrabuddhe, Sneha M. Pinto, Srikanth Srinivas Manda, Santosh Renuse, H. C. Manju, Mohammed Abdul Lateef Zameer, Jyoti Sharma, Mariana Brait, Kotteazeth Srikumar, Juan Carlos Roa, M. Vijaya Kumar, K. V.Veerendra Kumar, T. S.Keshava Prasad, Girija Ramaswamy, Rekha Vijay KumarAkhilesh Pandey, Harsha Gowda, Aditi Chatterjee

Research output: Contribution to journalArticle

Abstract

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer.

Original languageEnglish (US)
Pages (from-to)336-345
Number of pages10
JournalCancer Biology and Therapy
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2015

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Keywords

  • In vitro labeling
  • Invasion
  • Mass spectrometry
  • Proliferation
  • Targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Subbannayya, Y., Syed, N., Barbhuiya, M. A., Raja, R., Marimuthu, A., Sahasrabuddhe, N., Pinto, S. M., Manda, S. S., Renuse, S., Manju, H. C., Zameer, M. A. L., Sharma, J., Brait, M., Srikumar, K., Roa, J. C., Kumar, M. V., Kumar, K. V. V., Prasad, T. S. K., Ramaswamy, G., ... Chatterjee, A. (2015). Calcium calmodulin dependent kinase kinase 2 - A novel therapeutic target for gastric adenocarcinoma. Cancer Biology and Therapy, 16(2), 336-345. https://doi.org/10.4161/15384047.2014.972264