TY - JOUR
T1 - Calcium calmodulin dependent kinase kinase 2 - A novel therapeutic target for gastric adenocarcinoma
AU - Subbannayya, Yashwanth
AU - Syed, Nazia
AU - Barbhuiya, Mustafa A.
AU - Raja, Remya
AU - Marimuthu, Arivusudar
AU - Sahasrabuddhe, Nandini
AU - Pinto, Sneha M.
AU - Manda, Srikanth Srinivas
AU - Renuse, Santosh
AU - Manju, H. C.
AU - Zameer, Mohammed Abdul Lateef
AU - Sharma, Jyoti
AU - Brait, Mariana
AU - Srikumar, Kotteazeth
AU - Roa, Juan Carlos
AU - Kumar, M. Vijaya
AU - Kumar, K. V.Veerendra
AU - Prasad, T. S.Keshava
AU - Ramaswamy, Girija
AU - Kumar, Rekha Vijay
AU - Pandey, Akhilesh
AU - Gowda, Harsha
AU - Chatterjee, Aditi
N1 - Publisher Copyright:
© 2015 Taylor & Francis Group, LLC.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - In vitro labeling
KW - Invasion
KW - Mass spectrometry
KW - Proliferation
KW - Targeted therapy
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U2 - 10.4161/15384047.2014.972264
DO - 10.4161/15384047.2014.972264
M3 - Article
C2 - 25756516
AN - SCOPUS:84924598527
SN - 1538-4047
VL - 16
SP - 336
EP - 345
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 2
ER -