PMID- 25756516 OWN - NLM STAT- MEDLINE DCOM- 20151130 LR - 20220309 IS - 1555-8576 (Electronic) IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 16 IP - 2 DP - 2015 TI - Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma. PG - 336-45 LID - 10.4161/15384047.2014.972264 [doi] 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. FAU - Subbannayya, Yashwanth AU - Subbannayya Y AD - a Institute of Bioinformatics ; International Technology Park ; Bangalore , India. FAU - Syed, Nazia AU - Syed N FAU - Barbhuiya, Mustafa A AU - Barbhuiya MA FAU - Raja, Remya AU - Raja R FAU - Marimuthu, Arivusudar AU - Marimuthu A FAU - Sahasrabuddhe, Nandini AU - Sahasrabuddhe N FAU - Pinto, Sneha M AU - Pinto SM FAU - Manda, Srikanth Srinivas AU - Manda SS FAU - Renuse, Santosh AU - Renuse S FAU - Manju, H C AU - Manju HC FAU - Zameer, Mohammed Abdul Lateef AU - Zameer MA FAU - Sharma, Jyoti AU - Sharma J FAU - Brait, Mariana AU - Brait M FAU - Srikumar, Kotteazeth AU - Srikumar K FAU - Roa, Juan Carlos AU - Roa JC FAU - Vijaya Kumar, M AU - Vijaya Kumar M FAU - Kumar, K V Veerendra AU - Kumar KV FAU - Prasad, T S Keshava AU - Prasad TS FAU - Ramaswamy, Girija AU - Ramaswamy G FAU - Kumar, Rekha Vijay AU - Kumar RV FAU - Pandey, Akhilesh AU - Pandey A FAU - Gowda, Harsha AU - Gowda H FAU - Chatterjee, Aditi AU - Chatterjee A LA - eng GR - HHSN268201000032C/PHS HHS/United States GR - U24CA160036/CA/NCI NIH HHS/United States GR - U54GM103520/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proteome) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Adenocarcinoma/drug therapy/*metabolism MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Calcium-Calmodulin-Dependent Protein Kinase Kinase/antagonists & inhibitors/genetics/*metabolism MH - Cell Line, Tumor MH - Cell Proliferation MH - Enzyme Activation MH - Gene Expression MH - Gene Silencing MH - Humans MH - Immunohistochemistry MH - Molecular Targeted Therapy MH - Protein Kinase Inhibitors/*pharmacology/therapeutic use MH - Proteome MH - Proteomics MH - Reproducibility of Results MH - Stomach Neoplasms/drug therapy/*metabolism PMC - PMC4622549 OTO - NOTNLM OT - LC-MS/MS, Liquid chromatography-tandem mass spectrometry OT - PSM, Peptide spectrum match OT - SCX, Strong cation exchange chromatography OT - iTRAQ, Isobaric tags for relative and absolute quantitation OT - in vitro labeling OT - invasion OT - mass spectrometry OT - proliferation OT - siRNA, short interfering RNA OT - targeted therapy EDAT- 2015/03/11 06:00 MHDA- 2015/12/15 06:00 PMCR- 2016/03/10 CRDT- 2015/03/11 06:00 PHST- 2015/03/11 06:00 [entrez] PHST- 2015/03/11 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2016/03/10 00:00 [pmc-release] AID - 972264 [pii] AID - 10.4161/15384047.2014.972264 [doi] PST - ppublish SO - Cancer Biol Ther. 2015;16(2):336-45. doi: 10.4161/15384047.2014.972264.