Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2)-Mediated Carcinogenesis in Gastric Cancer

Gastric cancer is the fifth most
common cancer and the third leading
cause of cancer-related death worldwide. We showed previously that
calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a serine–threonine
kinase, is highly expressed in gastric cancer and leads to progression.
In the present study, we identified the molecular networks involved
in CAMKK2-mediated progression of gastric adenocarcinoma. Treatment
of gastric cancer cell lines with a CAMKK2 inhibitor, STO-609, resulted
in decreased cell migration, invasion, and colony-forming ability
and a G1/S-phase arrest. In addition, tandem mass tag (TMT)-based
quantitative proteomic analysis resulted in the identification of
7609 proteins, of which 219 proteins were found to be overexpressed
and 718 downregulated (1.5-fold). Our data identified several key
downregulated proteins involved in cell division and cell proliferation,
which included DNA replication licensing factors, replication factor
C, origin recognition complex, replication protein A and GINS, and
mesenchymal markers, upon CAMKK2 inhibition. Immunoblotting and immunofluorescence
results showed concordance with our mass spectroscopy data. Taken
together, our study supports CAMKK2 as a novel therapeutic target
in gastric cancer.