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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2)-Mediated
Mohd Altaf Najar1, Prashant Kumar Modi1, Poornima Ramesh1
1Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India.
Abstract:
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.
Insights
Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) drives gastric cancer progression. Inhibiting CAMKK2 halts cancer cell growth and invasion, revealing it as a promising therapeutic target for gastric adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer is a leading cause of cancer death globally.
- Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is highly expressed in gastric cancer and promotes its progression.
- Understanding CAMKK2's molecular networks is crucial for developing targeted therapies.
Purpose of the Study:
- To identify the molecular networks regulated by CAMKK2 in gastric adenocarcinoma.
- To investigate the therapeutic potential of inhibiting CAMKK2 in gastric cancer.
- To elucidate the downstream effects of CAMKK2 inhibition on cellular processes.
Main Methods:
- Treatment of gastric cancer cell lines with the CAMKK2 inhibitor STO-609.
- Analysis of cell migration, invasion, colony formation, and cell cycle.
- Tandem mass tag (TMT)-based quantitative proteomic analysis.
- Validation using immunoblotting and immunofluorescence.
Main Results:
- STO-609 treatment decreased gastric cancer cell migration, invasion, and colony formation, inducing G1/S-phase arrest.
- Proteomic analysis identified significant changes in protein expression upon CAMKK2 inhibition.
- Key downregulated proteins involved in cell division, DNA replication, and mesenchymal markers were identified.
Conclusions:
- CAMKK2 plays a significant role in gastric cancer progression.
- Inhibition of CAMKK2 effectively suppresses cancer cell proliferation and invasion.
- CAMKK2 represents a novel and promising therapeutic target for gastric cancer treatment.
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