title: Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.
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.
authors.affiliation: a Institute of Bioinformatics ; International Technology Park ; Bangalore , India.
authors.forename: Yashwanth
authors.initials: Y
authors.lastname: Subbannayya
authors.forename: Nazia
authors.initials: N
authors.lastname: Syed
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Barbhuiya
authors.forename: Remya
authors.initials: R
authors.lastname: Raja
authors.forename: Arivusudar
authors.initials: A
authors.lastname: Marimuthu
authors.forename: Nandini
authors.initials: N
authors.lastname: Sahasrabuddhe
authors.forename: Sneha M
authors.initials: SM
authors.lastname: Pinto
authors.forename: Srikanth Srinivas
authors.initials: SS
authors.lastname: Manda
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.forename: H C
authors.initials: HC
authors.lastname: Manju
authors.forename: Mohammed Abdul Lateef
authors.initials: MA
authors.lastname: Zameer
authors.forename: Jyoti
authors.initials: J
authors.lastname: Sharma
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.forename: Kotteazeth
authors.initials: K
authors.lastname: Srikumar
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
authors.forename: M
authors.initials: M
authors.lastname: Vijaya Kumar
authors.forename: K V Veerendra
authors.initials: KV
authors.lastname: Kumar
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: Girija
authors.initials: G
authors.lastname: Ramaswamy
authors.forename: Rekha Vijay
authors.initials: RV
authors.lastname: Kumar
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020543:Proteome; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases
keywords: LC-MS/MS, Liquid chromatography-tandem mass spectrometry; PSM, Peptide spectrum match; SCX, Strong cation exchange chromatography; iTRAQ, Isobaric tags for relative and absolute quantitation; in vitro labeling; invasion; mass spectrometry; proliferation; siRNA, short interfering RNA; targeted therapy